BioFiles

Volume 4, Number 3

Life Science

Antibiotics for Research Applications

Antimicrobial Peptides Antifungals

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Peptides perturbing bacterial cell wall and extracting liposomal sphere, resulting in cell death.

BioFiles
Volume 4, Number 3

Life Science

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Table of Contents
Introduction Antimicrobial Peptides
Bacteriocins Insect RAMPs Mammalian RAMPs Bacterial Cell Killing Mechanisms

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5 5 6 7

Antifungals
Antifungal Mechanisms of Action

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10 11 12 13 13 14 15

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Drug Resistance by Fungi Antifungals that Bind Ergosterol or Inhibit Biosynthesis Inhibits β-(1→3)Glucan Synthesis Chitin Synthesis Inhibitors Interferes with DNA, RNA, or Protein Synthesis Additional Antifungal Compounds

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The Antibiotic Web Resource
The antibiotic web resource allows you to conveniently browse antibiotic products by several different categories:
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Alphabetically Application Chemical Structure

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Mechanism of Action Spectrum of Activity
Technical Content: Vicki Caligur, B.Sc. and Chloe McClanahan, B.Sc.

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Solubility Solution Stability Working Concentration

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Introduction
Chloe McClanahan Product Manager, Biochemistry chloe.mcclanahan@sial.com This issue of BioFiles provides insight into antibacterial and antifungal resistance. Antifungal resistance may be just as alarming as antibacterial resistance. A reported mortality rate for patients with immunity inflicting diseases that develop resistant fungal infections is 50–90%. Unfortunately, the elevated concern about resistance has not resulted in an abundance of antibiotics in the pharmaceutical pipeline due to high developmental costs and commercialization barriers. However, there is currently promising research being done to better understand the mechanisms and interactions of antimicrobial peptides and antifungal compounds in order to develop new, antibiotic drug candidates. The article on page 4 provides an informative overview of the characteristics, mechanisms of action and types of ribosomally synthesized antimicrobial peptides (RAMPs) that either solely provide or contribute to the innate pathogenic defense system for many species. RAMPs are of growing interest because of continual RAMP discoveries and their lack of resistant isolates. The article on page 10 provides background information on the structural components of the fungal cell wall to aid in the understanding of the damaging functionality of antifungal compounds, along with a brief synopsis of drug resistance by fungal species. Antimicrobial peptides and antifungals available from Sigma® Life Science are found within this issue of BioFiles. Please visit the BioBlog to see video on bacterial quorum sensing and its potential for new antibiotic therapeutics. Visit sigmabioblogs.com In addition to our antimicrobial peptides and antifungals, Sigma Life Science is continuously expanding our product offering based on research interest and customer demand. New antibiotic products are described on page 16, while our popular ready made antibiotic solutions are listed on page 19. If you have a new product suggestion for an antibiotic, please visit sigma.com/product_suggestions. To help guide researchers in locating the most appropriate antibiotics, we have created the online Antibiotic Selector to aid in the selection and usability of research antibiotics. Antibiotic Selector Please see page 21 for an Antibiotic Selector tutorial. Additionally, a companion selection poster with application, preparation, usage concentration, solution stability, and mechanistic information for the most commonly used research antibiotics is available. Please visit sigma.com/antibiotics to use the new Antibiotic Selector.

Introduction

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Antimicrobial Peptides
With bacterial resistance and emerging infectious diseases becoming potential threats to humans, ribosomally synthesized antimicrobial peptides have become a promising focus area in antibiotic research. Antimicrobial peptides are classified as either non-ribosomally synthesized peptides or ribosomally synthesized peptides (RAMPs). Non-ribosomally synthesized peptides are found in bacteria and fungi. These antimicrobial peptides are assembled by peptide synthetases as opposed to ribosomal-supported synthesis. Gramicidin, bacitracin, polymyxin B, and vancomycin are examples of non-ribosomally synthesized antimicrobial peptides. These antibiotics are proven to be effective research tools, but compared to RAMPs they are disadvantageous for novel applications due to emerging bacterial resistance, for example vancomycin-resistant Staphylococcus aureus and enterococci. RAMPs are derived from a diverse range of species, from prokaryotes to humans. Antimicrobial peptides comprise a host’s natural defense against the daily exposure to millions of potential pathogens. These peptides may also possess antiviral, antiparasitic, and antineoplastic activities. Over 500 RAMPs have been described in the literature. Their unique antibiotic spectrum is determined by amino acid sequence and structural conformation. RAMPs are gene-encoded peptides consisting of 12-50 amino acids with very little genetic overlap. A lack of sequence homology between RAMPs is indicative of evolutionary optimization of form and function in the species environment. RAMPs are typically cationic peptides with at least half of the amino acid residues being hydrophobic and a smaller number of neutral or negatively charged residues. Their amphipathic structure with opposing hydrophobic and lipohphilic faces aids in the perturbation of the bacterial cell wall. The mechanism of action of a RAMP involves peptide binding to the bacterial cell surface, conformational change to the peptide, aggregation of multiple peptide monomers, and pore formation through the bacterial cell wall. RAMPs bind to lipopolysaccharides in the negatively-charged, Gram-negative bacterial outer cell wall or to the acidic polysaccharides of the Gram-positive bacterial outer cell wall. After binding, permeabilization of the bilayer membrane occurs by transient pore creation. Permeabilization leads to a leakage of cell components and cell death. There are several models of permeabilization although the precise mechanism is unknown. Three permeabilization models are termed barrel-stave, thoroidal, and carpet. Figure 1 depicts bacterial cell wall perturbation by a RAMP.

Antimicrobial Peptides

Figure 1. Antimicrobial peptide perturbation of the bacterial cell wall via the carpet model mode of action.

RAMPs are ideal candidates for clinical antimicrobial use because they: 1) Are active against antibiotic-resistant isolates 2) Do not select for resistant mutants and have limited natural bacterial resistance 3) Are synergistic with conventional antibiotics, specifically against resistant mutants 4) Are proven to kill bacteria in animal models 5) Kill rapidly 6) Provide benefical, supplementary activities, for example sepsis inhibition Although RAMPs are ideal clinical candidates, their diverse structural variation makes it difficult to predict RAMP activity in vivo; therefore, it is challenging to design functional synthetic mimetics. Small changes in peptide sequence or conformation can lead to major in vivo differences in antimicrobial and cytotoxicity levels. An optimal in vitro minimum inhibitory concentration (MIC) against a range of bacterial organisms is 18 μg/ml. However, it is challenging to predict an ideal in vivo MIC from this in vitro MIC. In order to obtain MIC, specificity, stability and toxicity information, novel, synthetic antimicrobial peptides have been designed using data from RAMP-related, bioinformatic databases (see Table 1). Production costs, protease susceptibility, and potential resistance from widespread use are additional concerns in the transition of RAMP application from a research to clinical setting.

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Antimicrobial Peptide Databases BAGEL Molecular Genetics Dept., University of Groningen, The Netherlands PhytAMP ISSBAT Institute, Tunisia and INAF Institute, Laval University, Canada Antimicrobial Peptide Database, Version 2 UNMC Eppley Cancer Center, University of Nebraska Medical Center, USA SAPD Haartman Institute, Helsinki University, Finland Defensins Knowledgebase Bioinformatics Institute, Singapore and Singapore Eye Research Institute

Information Available Bacteriocin genome location tool. Structural information and phylogenetic tree for ~270 natural, plant antimicrobial peptides. Structural and functional information for 1,000+ antibacterial peptides. Synthetic antibiotic peptide database. Sequence, structural and activity information for ~360 defensins.

Web Site http://bioinformatics.biol.rug.nl/websoftware/ bagel/bagel_start.php http://phytamp.pfba-lab-tun.org/main.php http://aps.unmc.edu/AP/main.html http://oma.terkko.helsinki.fi:8080/~SAPD http://defensins.bii.a-star.edu.sg/

Table 1. Antimicrobial Peptide Online Databases

Antimicrobial Peptides

Bacteriocins
Bacteriocins are non-pathogenic, antimicrobial peptides or proteins secreted by both Gram-positive and Gram-negative bacteria. Bacteriocins prevent the growth of similar bacterial strains but avoid damaging the host bacteria by selectively killing based on post-transcriptional modification and/or specific immunity mechanisms. Unlike the wide activity spectrum of conventional antibiotics, bacteriocins have a narrow activity spectrum. Additionally bacteriocins play a role in the regulation of signaling, virulence, and sporulation. Nisin (Cat. No. N5764) is classified as a Class I, Type A lantibiotic. It is produced by Gram-positive, lactic acid fermentation bacteria and contains several atypical modified amino acids: thioetherbridged lanthionine, methyllanthionine, didehydroalanine and didehydroaminobutyric acid. Class I, Type A lantibiotics are elongated peptides that exhibit a range of activities including pore formation in bacterial bilayers while Class I, Type B lantibiotics are smaller, globular negatively charged or neutral peptides that inhibit specific enzymes. Class I, Type B lantibiotics include cinnamycin (Cat. No. C5241) and duramycin (Cat. No. D3168). An interesting subgroup of the non-lantibiotic bacteriocins is the Class IIa pediocin-like peptides. Pediocin (Cat. No. P0098) has been studied for its activity against pathogenic bacteria such as Listeria monocytogenes. Although the genetic sequences of bacteriocins are not conserved, bacteriocin genes are often positioned near genes that aid in their production, for example transporter genes. BAGEL is a bacteriocin genome location tool developed and maintained by the Molecular Genetics Department at the University of Groningen, The Netherlands. This software is available for both academic and commercial use at http://bioinformatics.biol.rug.nl/websoftware/ bagel/bagel_start.php. Many of the bacteriocins are being studied for their application in food preservation. This methodology reduces requirements for potentially carcinogenic pesticides and heat treatments that reduce nutritional properties in food. Bacteriocins may function as alternatives to conventional antibiotics that have been impacted by resistant strains. Millette, M. et al. recently demonstrated that nisin- and pediocin-producing bacteria reduced intestinal colonization by vancomycin-resistant Enterococci in vivo.

Insect RAMPs
Cecropin is a type of RAMP secreted within insects and active against Gram-negative bacteria. Cecropin A (Cat. No. C6830) is extracted from the hemolymph of the silk moth (Hyalophora cecropia) but has also been identified in porcine intestine. Antimicrobial peptides are often components of insect venoms, for example melittin from bee venom (Cat. No. M2272). It has been proposed that in primitive insect species RAMPs replace immune system processes, for example cytokine release, that characterize the bactericidal response in higher organisms. Drosophila synthesize different antimicrobial peptides in response to various infecting organisms. Kallio, J. et al. reported that RNAi targeting of several immune response genes in Drosophila caused altered antimicrobial peptide synthesis and identified involvement of the JNK signaling pathway in RAMP production.

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Mammalian RAMPs
Although bacteriocins, insect, and mammalian RAMPs are similar in their bactericidal activity, the mammalian RAMPs also function as regulatory molecules in the host species’ immune response. Defensins are a group of cationic, mammalian RAMPs that are commonly found on the skin, ear, epithelium, tongue, lung, and other surfaces frequently exposed to environmental pathogens. Phagocytic and epithelial cells, lymphocytes, and keratinocytes produce defensins. Figure 2 is an immunohistochemical staining of defensin-5 within respiratory epithelial cells using Prestige Antibodies® Anti-DEFA5 antibody, produced in rabbit (Cat. No. HPA015775). Defensins are constitutively expressed and stored in granules without external stimuli. However, increased levels of expression may be induced by proinflammatory cytokines, exogenous bacterial or LPS treatment. Like the bacteriocins, defensins consist of variable amino acid residue composition. The two classes of defensins are defined by structure. The human α-defensins have three intramolecular cysteine bonds whereas the larger β-defensins (Cat. Nos. D9565, β-defensin 1 and D9690, β-defensin 2) consist of three antiparallel β-sheets and a unique disulfide bridge pattern connecting six cysteine residues. In addition to antimicrobial and antiviral activities, α-defensins inactivate LPS binding, regulate complement activation, and function as an adjuvant in mice. β-defensins induce prostaglandin production and play a regulatory role in the adaptive immune responses by functioning as chemoattractants for T lymphocytes as well as for immature dendritic cells via signaling through a chemokine receptor.

References: Pag, U. et al., In vitro activity and mode of action of diastereometric antimicrobial peptides against bacterial clinical isolates. JAC, 53, 230-239 (2004). Papagianni, M., Ribosomally synthesized peptides with antimicrobial properties: biosynthesis, structure, function, and applications. Biotech. Advances, 21, 465-499 (2003). Gunn, J.S., Bacterial modification of LPS and resistance to antimicrobial peptides. J. Endotoxin Res., 7, 57-62 (2001). Nicholson, J.K. et al., The challenges of modeling mammalian biocomplexity. Nat. Biotechnol., 22, 1268-1274 (2004). Palffy, R. et al., On the physiology and pathophysiology of antimicrobial peptides. Mol. Med., 15, 51-59 (2009). Hancock, R. and Chapple, D., Peptide antibiotics. Antimicrob. Agents Chemother., 43, 1317-1323 (1999). Hancock, R. and Scott, M. The role of antimicrobial peptides in animal defense. PNAS, 97, 8856-8861 (2000). Drider, D. et al., The continuing story of class IIa bacteriocins. Microbiol. Mol. Biol. Rev., 70, 564-582 (2006). Holtsmark, I. et al., Bacteriocins from plant pathogenic bacteria. FEMS Microbiol. Lett., 280, 1-7 (2007). Chen, H. and Hoover, D.G. Bacteriocins and their food applications. Comprehensive Reviews in Food Science and Food Safety, 2, 82-100 (2003). Galvez, A. et al., Application of bacteriocins in the control of foodborne pathogenic and spoilage bacteria. Crit. Rev. Biotechnol., 28, 125-152 (2008). Galvez, A. et al., Bacteriocin-based strategies for food biopreservation. Int. J. Food Microbiol., 120, 51-70 (2007). Brumfitt, W. et al., Nisin, alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. J. Antimicrob. Chemother., 50, 731-734, (2002). Millette, M et al., Capacity of human nisin- and pediocin-producing lactic acid bacteria to reduce intestinal colonization by vancomycin-resistant enterococci. Appl. Environ. Microbiol., 74, 1997-2003 (2008). Montesinos, E., Antimicrobial peptides and plant disease control. FEMS Microbiol. Lett., 270, 1-11 (2007). Buckling, A. and Brockhurst, M. Microbiology: RAMP resistance. Nature, 438, 170-171 (2005). Kallio, J. et al., Functional analysis of immune response genes in Drosophila identifies JNK pathway as a regulator of antimicrobial peptide gene expression in S2 cells. Microbes and Infection, 7, 811-819 (2005). Komatsuzawa, H. et al., Innate defences against methicillin-resistant Staphylococcus aureus (MRSA) infection. J. Pathol., 208, 249-260 (2006). Meade, K.G. et al., Directed alteration of a novel bovine β-defensin to improve antimicrobial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Antimicrob. Agents, 32, 392-397 (2008). Oppenheim, J.J. et al., Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann. Rheum. Dis., 62, ii17-ii21 (2003). Yang, D. et al., The role of mammalian antimicrobial peptides and proetins in awakening of innate host defenses and adaptive immunity. Cell Mol. Life Sci., 58, 978-989 (2001). Yang, D. et al., β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science, 286, 525-528 (1999).

Antimicrobial Peptides

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Figure 2. Immunohistochemical staining of human nasopharynx shows cytoplasmic and membranous positivity in respiratory epithelial cells using Prestige Antibodies® Anti-DEFA5 (Cat. No. HPA015775).

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Bacterial Cell Killing Mechanisms
The diversity of structure within antimicrobial peptides results in an essential, innate defense system for both simple and complex organisms. Although the antimicrobial peptides have unique structural properties, they can be simply categorized by their killing action. Antimicrobial peptides typically use one of the following killing mechanisms: cell membrane interference, cell wall synthesis interference, protein synthesis interference, protein inhibition and nucleic acid inhibition.

Cell Membrane Interference
Name Cecropin A, ≥97% (HPLC), powder Cecropin B, ≥97% (HPLC), powder Cecropin P1 Porcine, ≥95% (HPLC), powder Cinnamycin, >95% (HPLC), solid Description Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. Cinnamycin (Ro 09-0198) is a tetracylic peptide antibiotic (19 amino acids) that binds specifically to the cell surface phosphatidylethanolamine and subsequently induces cytolysis. This is a rare example of a small peptide binding to a particular lipid (1:1 complex). Cinnamycin belongs to the duramycin-type lantibiotics and contains the unusual thioether lanthionine amino acids. Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity. Antimicrobial spectrum: Gram-negative bacteria. Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity. Antimicrobial spectrum: Gram-negative bacteria. Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity. Antimicrobial spectrum: Gram-negative bacteria. This is an endogenous antibiotic peptide and monocyte chemotactic peptide produced by human neutrophils. Defensins are a family of 3-4 kDa (29-34 amino acids) peptides found in the granules of mammalian phagocytes. The members of this family are variably arginine-rich and share six conserved cysteine residues that participate in intramolecular disulfide bonds. This is an endogenous antibiotic peptide and monocyte chemotactic peptide produced by human neutrophils. Defensins are a family of 3-4 kDa (29-34 amino acids) peptides found in the granules of mammalian phagocytes. The members of this famuly are variably arginine-rich and all share 6 conserved cysteine residues that participate in intramolecular disulfide bonds. Cat. No. C6830-.1MG C6830-.5MG C1796-.1MG C1796-.5MG C7927-.1MG C7927-.5MG C5241-1MG

Antimicrobial Peptides

Colistin sulfate salt, activity: ≥15,000 units/mg

C4461-100MG C4461-1G C1511-10MU C1511-100MU 27655-1G 27655-5G D2043-25UG

Colistin sodium methanesulfonate, activity: ~11,500 units/mg Colistin sodium methanesulfonate, BioChemika, from Bacillus colistinus Defensin HNP-1 human, ≥80% (HPLC)

Defensin HNP-2 human, ≥95% (HPLC)

D6790-25UG

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Cell Membrane Interference, continued
Name Indolicidin, ≥97% (HPLC) Magainin I, ≥97% (HPLC) Description Exhibits potent antimicrobial activity in vitro against bacteria and fungi. Antibiotic peptide. Thought to preferentially bind to anionic phospholipids abundant in bacterial membranes with the formation of dynamic peptide-lipid supramolecular pore and cell permeabilization, magainins are positively charged and amphiphatic. Binding to artificial neutral membranes has also been demonstrated. Antibiotic peptide. Magainins are positively charged and amphiphatic. Thought to preferentially bind to anionic phospholipids abundant in bacterial membranes with the formation of dynamic peptide-lipid supramolecular pore and cell permeabilization. Binding to artificial neutral membranes has also been demonstrated. Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane. Antimicrobial spectrum: Gram-negative bacteria. Pediocins are class IIa bacteriocins that are produced by Pediococcus sp. They are cationic peptides that show strong activity against pathogenic bacteria such as Listeria monocytogenes, Clostridicum perfringes, Enterococcus faecalis, and Staphylococcus aureus. This antimicrobial action of pediocins is based on interaction with the cytoplasmic membrane, resulting in pore formation and cell death. Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane. Antimicrobial spectrum: Gram-negative bacteria. Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane. Antimicrobial spectrum: Gram-negative bacteria. Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane. Antimicrobial spectrum: Gram-negative bacteria. Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mode of Action: Binds to and interferes with the permeability of the cytoplasmic membrane. Antimicrobial spectrum: Gram-negative bacteria. K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction. K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction. K+-selective ionophoric cyclodepsipeptide; potassium ionophore which uncouples oxidative phosphorylation, induces apoptosis in murine thymocytes, inhibits NGF-induced neuronal differentiation and antagonizes ET-induced vasoconstriction. Cat. No. I0144-.1MG M7152-.1MG M7152-.5MG M7152-1MG M7402-.1MG M7402-.5MG M7402-1MG N5764-1G N5764-5G N5764-25G P0098-50UG

Magainin II, ≥97% (HPLC)

Antimicrobial Peptides

Nisin from Lactococcus lactis, 2.5% (balance sodium chloride and denatured milk solids)

Pediocin from Pediococcus acidilactici, ≥95% (HPLC), buffered aqueous solution 8

Polymyxin B solution, BioChemika, 1 mg/mL in H2O Polymyxin B sulfate, meets USP testing specifications, powder

81271-10ML P0972-1MU P0972-10MU P0972-50MU P1004-1MU P1004-5MU P1004-10MU P1004-25MU P1004-50MU P4932-1MU P4932-5MU

Polymyxin B sulfate salt, activity: ≥6,000 USP units/mg

Polymyxin B sulfate salt, powder, cell culture tested

Polymyxin B sulfate salt, Biotechnology Performance Certified

P4119-10MU P4119-25MU P4119-50MU V0627-10MG V0627-25MG V0627-100MG V0627-500MG 94675-10MG 94675-100MG 94675-500MG V3639-5ML

Valinomycin, ≥98% (TLC), ≥90% (HPLC), solid

Valinomycin, BioChemika, ≥98.0% (TLC)

Valinomycin, Ready Made Solution, ~1 mg/mL in DMSO, 0.2 μm filtered

Cell Wall Synthesis Interference
Name Bacitracin, from Bacillus licheniformis, activity: ≥50,000 U/g Bacitracin, from Bacillus licheniformis, BioChemika, activity: ≥60000 U/g (Potency) Bacitracin zinc salt, from Bacillus licheniformis, activity: ~70,000 U/g Vancomycin hydrochloride from Streptomyces orientalis, potency: ≥900 μg per mg (as vancomycin base) Vancomycin hydrochloride from Streptomyces orientalis, Biotechnology Performance Certified Description Peptide antibiotic. Antimicrobial spectrum: Gram-positive bacteria. Mode of Action: Inhibits bacterial cell wall synthesis by inhibiting dephosphorylation of lipid pyrophosphate. Peptide antibiotic. Antimicrobial spectrum: Gram-positive bacteria. Mode of Action: Inhibits bacterial cell wall synthesis by inhibiting dephosphorylation of lipid pyrophosphate. Peptide antibiotic. Antimicrobial spectrum: Gram-positive bacteria. Mode of Action: Inhibits bacterial cell wall synthesis by inhibiting dephosphorylation of lipid pyrophosphate. Glycopeptide antibiotic Mode of action: interferes with cell wall synthesis Antimicrobial spectrum: Gram-positive bacteria Glycopeptide antibiotic Mode of action: interferes with cell wall synthesis Antimicrobial spectrum: Gram-positive bacteria Cat. No. B0125-50KU B0125-250KU B0125-1250KU 11702-5G 11702-25G B5150-250KU B5150-1250KU V2002-100MG V2002-250MG V2002-1G V2002-5G V1764-250MG V1764-1G

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Protein Synthesis Interference or Inhibition
Name Actinonin Amastatin hydrochloride hydrate, ≥97% (HPLC) Description Inhibitor of leucine aminopeptidase. Amastatin is a slow, tight-binding inhibitor of aminopeptidases. It inhibits cytosolic leucine aminopeptidase (EC.3.4.11.1), microsomal aminopeptidase M (EC.3.4.11.2) and bacterial leucine aminopeptidase (EC.3.4.11.10). It is less effective against aminopeptidase A (EC 3.4.11.7), the enzyme that converts Angiotensin II to Angiotensin III. Effective concentration: 1-10 μM. Cat. No. A6671-10MG A6671-25MG A1276-250UG A1276-.5MG A1276-1MG A1276-5MG A1276-10MG A1276-25MG A8674-25MG A8674-50MG A8674-100MG A6191-1MG A6191-5MG A6191-25MG A6191-100MG D3168-10MG E7280-100UG

Antimycin A from Streptomyces sp.

Inhibitor of electron transfer at complex III. Induces apoptosis.

Antimicrobial Peptides

Antipain dihydrochloride from microbial source

Isolated from a microbial source, antipain hydrochloride is a reversible inhibitor of serine/cysteine proteases and some trypsin-like serine proteases. Its action resembles leupeptin; however, its plasmin inhibition is less and its cathepsin A inhibition is more than that observed with leupeptin. Polypeptide antibiotic which enhances chloride secretion in airway epithelium; used in studies of cystic fibrosis Exhibits co-existant antimicrobial and antiproteolytic activities. Antimicrobial spectrum: Gram-positive and Gram-negative bacteria. Gramicidin A is a polypeptide antibiotic that forms single ion monovalent cation channels in biological membranes. Linear polypeptide antibiotic, a mixture of gramicidin A, B, C, and D. Gramicidin D, a channel-forming ionophore that flip-flops slowly across the membrane is a known Pgp substrate and surprisingly was found to inhibit Pgp ATPase activity. This inhibition was reversed by other Pgp substrates suggesting a common drug binding site among MDR substrate-type drugs and chemosensitizers. Naturally occuring polypeptide antibiotic with Tyr at position 11; functions as a transmembrane ion channel. Peptide antibiotic that prevents the binding of elongation factor G (EF-G) and GTP to the 50S ribosomal subunit.

Duramycin from Streptoverticillium cinnamoneus, 90-95% Elafin human, >90% (by MS, HPLC and SDS-PAGE), recombinant, expressed in Saccharomyces cerevisiae Gramicidin A from Bacillus brevis, BioChemika, ≥90% (HPLC) Gramicidin from Bacillus aneurinolyticus (Bacillus brevis), Linear polypeptide antibiotic complex. A mixture of gramicidins A, B, C, and D. Gramicidin C from Bacillus brevis, BioChemika, ~90% (HPLC) Thiostrepton from Streptomyces azureus, ≥90% (HPLC)

50845-100MG 50845-500MG G5002-100MG G5002-500MG G5002-1G G5002-5G 50847-10MG 50847-50MG T8902-1G

Nucleic Acid Inhibition
Name Actinomycin D, from Streptomyces sp., ~98% (HPLC) Description An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes. An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes. An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes. Mode of Action: Complexes with DNA and interferes with RNA synthesis. An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. For cell culture applications, actinomycin D is used as a selection agent and is used in banding techniques to differentiate between different regions of chromosomes. Cat. No. A1410-2MG A1410-5MG A1410-10MG A1410-25MG A1410-100MG A4262-2MG A4262-5MG A4262-10MG A4262-25MG A9415-2MG A9415-5MG A9415-10MG A9415-25MG A5156-1VL

Actinomycin D, from Streptomyces sp., ~95% (HPLC)

Actinomycin D, ≥95%, from Streptomyces sp., cell culture tested

Actinomycin D–Mannitol, lyophilized powder 1 mg actinomycin D and 49 mg mannitol per vial

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Antifungals
Antifungal compounds have been overshadowed by antibacterials in research interest and application due to the greater impact bacterial infections have had on health. Resistance to antibacterial drugs and the resultant clinical impact is of widespread concern regarding public health. However, resistance by pathogenic fungal infections to drug treatment has become more common in the last 20 years as well. Some mechanisms of the development of fungal resistance have similarities to those of the development of drug resistance in bacteria, and knowledge of those bacterial mechanisms is being applied to understanding fungal drug resistance. Several key antibiotic compounds function by targeting the integrity of the cell. Many compounds increase the porosity of the cell wall or membrane, or interfere with key steps in the synthesis of cell walls. While prokaryotic bacteria and eukaryotic fungi do not have identical cell wall and membrane components, there are corresponding lipids and key structural molecules. As a result, similar to antibacterials, most antifungal compounds work because they directly or indirectly damage the cell wall or cell membrane. The fungal cell wall is composed of multiple layers, with mannoproteins being predominantly expressed at the external surface (see Figure 1). An underlayer of β-glucan creates a supporting matrix for the mannoproteins and provides structural rigidity to the cell wall. The glucan structure is strengthened by frequent β(1→3) and additional β(1→6) linkages and by chitin interspersed with the β-glucan. Mannoproteins and glucan make up more than 80% of the cell wall composition, while chitin represents less than 2%. The plasma membranes of fungi are primarily composed of ergosterol, analogous to cholesterol in animal cells. Since ergosterol and cholesterol have sufficient structural differences, the majority of chemicals found to act as fungicides target ergosterol biosynthesis or cell membrane porosity and do not cross react with host cells.
Yeast Cell Wall

Antifungal Mechanisms of Action
Several reviews of antifungal compounds group them into structural classes and have associated certain structures with particular modes of actions. Examples of some of the key structures of fungicides are shown in Figure 2. The binding and synthesis of ergosterol, the major cell membrane component, are the targets for several antifungal structures. The azoles and triazoles interfere with the ergosterol biosynthesis pathway by inhibiting cytochrome P450-dependent 14α-demethylase and blocking the oxidative removal of 14α-methyl from lanosterol. This incomplete processing of lanosterol results in an increase in ergosterol precursors and a decrease in ergosterol, leading to structural changes in the lipid membrane. Azoles have also been reported to inhibit membrane-surface enzymes and lipid biosynthesis. Allylamines, of which terbinafine (Cat. No. T8826) is the most common example, also block ergosterol biosynthesis, but at an earlier step. Terbinatine inhibits the enzyme squalene epoxidase, which participates in the conversion of squalene to lanosterol. The resulting build-up of squalene is toxic to the fungal cell. A third structural class, polyenes, increases the permeability of the plasma membrane. Amphotericin B (Cat. No. A4888), a polyene with high affinity for sterol binding, is one of the most potent antifungal drugs; its mechanism produces pores in the membrane surface of the yeast, resulting in leakage of the cell contents. (Odds, et al., 2003).
a.
F

Antifungals

N

N N OH

F N

N N

b.

CH3 H N H • HCl

CH3 CH3 CH3

Yeast Cell Wall
Mannoprotein β-Glucan β-Glucan + Chitin Mannoprotein Membrane
Nystatin A1 HO CH3

c.
CH3 O O CH3 OH OH OH

OH

OH

OH COOH

OH O H

CH2

O H3C O OH H2N OH OH H

Figure 1. Structure of the yeast cell wall. The wall is primarily composed of mannoproteins and β-glucan that is linked (1→3) and (1→6). Ergosterol is the major lipid component of the underlying plasma membrane.

d.
H3C

HO

NH CO (CH2)14CH3 O N CH3 O H3C H HO H NH O H OH O H H N N H H OH O HO OH H N H

HO HO O H NH

Figure 2. Examples of antifungal structure classes. a. Fluconazole (triazole) b. Terbinafine (allylamine) c. Nystatin A1 (polyene) d. Aculeacin A (echinocandin).

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In addition to the plasma membrane and its lipid surface, fungicidal compounds may damage the cell wall of yeast. The major cell wall component β(1→3) glucan is the target of echinocandins and aculeacins such as aculeacin A (Cat. No. A7603). Echinocandins are semisynthetic lipopeptides that competitively inhibit β-glucan synthetase; the mechanism of action is not well defined but does not involve cytochrome P450 inhibition or P-glycoprotein transport (Kauffman and Carver, 2008). Chitin is a trace, critical component of the fungal cell wall, and some inhibitors of chitin synthesis demonstrate antifungal activity. Members of this family of antifungals (i.e., polyoxins and nikkomycins) have structures analogous to UDP-N-acetyl-Dglucosamine (UDP-GlcNAc). This nucleoside phosphate is a glycosyl donor substrate for chitin synthesis, and the antifungals act as competitive substrates to inhibit chitin synthetase (Hector, 1993). Not all antifungal compounds have known mechanisms of action, and some of them are relatively unique. While there are several antibacterials that function by preventing DNA or RNA replication, 5-fluorocytosine (Cat. No. F7129) is a novel antifungal in that its mechanism of action involves blocking DNA synthesis and inhibiting thymidylate synthetase. Sordarin (Cat. No. S1442) is one of the few compounds that selectively inhibit fungal protein synthesis. Other antifungal antibiotics target sphingolipid biosynthesis and electron transport (Gupte, et al., 2002). The mode of action of griseofulvin (Cat. No. G4753) is not completely clear, but it has been speculated that griseofulvin inhibits microtubule binding within the mitotic spindle, weakening the cell structure (Odds, et al., 2003).

Some research reports on antifungals have found greater efficacy with combinations of antifungal drugs that use different mechanisms of action. The same process has been applied to other compounds in looking for ways to overcome fungal resistance. A variety of immunosuppressive compounds, including cyclosporin and D-octapeptides (Monk, et al., 2005), have been tested and found to counteract antifungal resistance due to efflux pumps. Cernicka, et al. screened a synthetic compound library and identified a chemical that increased the sensitivity of a drug-resistant strain of S. cerevisiae to fluconazole (Cernicka, et al., 2007). The compound also increased sensitivity of the pathogenic yeasts Candida albicans and Candida glabrata that expressed efflux pumps. As drug resistance continues to develop in pathogenic fungi, there will be research to find ways to circumvent resistance and identify next-generation drugs. Understanding the cellular processes and resistance pathways can be applied to finding alternative compounds to the well-established azoles that are the prime targets of fungal efflux.
References: Cernicka, J., et al., Chemosensitisation of drug-resistant and drug-sensitive yeast cells to antifungals. Int. J. Antimicrob. Agents, 29, 170-8 (2007). Ghannoum, M.A. and Rice, L.B. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin. Microbiol. Rev., 12, 501-17 (1999). Gupte, M., et al., Antifungal antibiotics. Appl. Microbiol. Biotechnol., 58, 46-57 (2002). Hector, R.F. Compounds active against cell walls of medically important fungi. Clin. Microbiol. Rev., 6, 1-21 (1993). Kauffman, C.A. and Carver, P.L. Update on echinocandin antifungals. Semin. Respir. Crit. Care Med., 29, 211-9 (2008). Katzmann, D.J., et al., Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. J. Biol. Chem., 271, 23049-54 (1996). Monk, B.C., et al., Surface-active fungicidal D-peptide inhibitors of the plasma membrane proton pump that block azole resistance. Antimicrob. Agents Chemother., 49, 57-70 (2005). Monk, B.C. and Goffeau, A. Outwitting multidrug resistance to antifungals. Science, 321, 367-8 (2008). Odds, F.C., et al., Antifungal agents: mechanisms of action. Trends Microbiol., 11, 272-9 (2003). Rogers, B., et al., The pleitropic drug ABC transporters from Saccharomyces cerevisiae. J. Mol. Microbiol. Biotechnol., 3, 207-14 (2001). Vanden Bossche, H., et al. Antifungal drug resistance in pathogenic fungi. Med. Mycol., 36, Supp. 1.,119-28 (1998).

Antifungals

Drug Resistance by Fungi
Drug resistance in fungi, especially to azoles, is becoming more prevalent clinically, and the mechanisms of drug resistance are similar to those present in bacteria. Several factors contribute to multidrug resistance in yeasts, including the mutation of genes and overexpression of proteins that act as efflux pumps (Monk and Goffeau, 2008). Fungi contain both ATP-binding cassette (ABC) transporter and major facilitator superfamily (MFS) transporter gene families. The multidrug resistance process for fungi has been most analyzed for Saccharomyces cerevisiae, where it is called pleiotropic drug resistance (PDR) (Rogers, et al., 2001). In S. cerevisiae, point mutations occur in the genes for the transcription regulatory factors Pdr1p and Pdr3p. These mutations (called “gain-offunction” mutations) activated downstream target genes, including the ABC transporter genes and MFS transporter genes. The products of these genes are efflux pumps that transport drug compounds out of the cell, reducing the intracellular concentration to a sublethal level.

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Antifungals that Bind Ergosterol or Inhibit Biosynthesis
Name Amphotericin B from Streptomyces sp., ~80% (HPLC), powder Description Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast. Cat. No. A4888-100MG A4888-250MG A4888-500MG A4888-1G A4888-5G A4888-100G A2411-250MG A2411-1G A2411-5G A9528-50MG A9528-100MG A9528-500MG A9528-1G A9528-5G A2942-20ML A2942-50ML A2942-100ML C2389-5MG C2389-10MG C2389-50MG C6019-5G C6019-25G C6019-100G D4671-.1MG D4671-.5MG E4632-5G E4632-25G E4632-100G F9765-25MG F9765-50MG

Amphotericin B from Streptomyces sp., ~80% (HPLC), cell culture tested Amphotericin B solubilized, powder, γ-irradiated, cell culture tested

Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast. Polyene antifungal antibiotic from Streptomyces. Affinity for sterols, primarily ergosterols, of fungal cell membranes. Forms channels in the membranes, causing small molecules to leak out. Antimicrobial spectrum: fungi and yeast. Mode of Action: Interferes with fungal membrane permeability by forming channels in the membranes and causing small molecules to leak out. Mode of action: Interferes with fungal membrane permeability by forming channels in the membranes and causing small molecules to leak out. Antimicrobial spectrum: Yeasts and molds. Antibiotic and antifungal. Mode of action: Inhibits fatty acid synthetases, blocking production of fatty acids and sterols in both fungi and eukaryotes. Specific inhibitor of Ca2+-activated K+ channels. Antifungal azole. Antifungal mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, altering cell membrane permeability. Dermaseptin is a cationic, amphipathic antifungal peptide. Mode of action: Lysis of the cell membrane by interaction with membrane lipids. Highly potent antifungal activity at micromolar concentration. Econazole is an azole-based antifungal similar to ketoconazole. Its mechanism of action may involve inhibition of membrane enzymes, including cytochrome P450, and lipid biosynthesis. The bactericidal and inhibitory effects of several azole antifungal compounds, including econazole, against Mycobacterium smegmatis has been investigated. Filipin is a polyene macrolide antibiotic and antifungal. The antifungal mechanism of action is unclear but may be due to altering membrane permeability and associated functions via binding to membrane sterols. Filipin binds to membrane sterols such as cholesterol, and it both inhibits prion protein (PrP) endocytosis and causes the release of PrP from the plasma membrane. Fluconazole is an antifungal agent. It is highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethyllation. Fluconazole is a potent inhibitor of CYP2C9. Fluconazole interferes with fungal ergosterol synthesis and downregulates the metallothionein gene. Synthetic broad-spectrum triazole antifungal agent. Mode of action: Inhibits cytochrome P450 dependent enzymes including 14α-demethylase. The inhibition results in prevention of the biosynthesis of ergosterol, a critical fungal cell wall component in fungi. First generation antifungal azole. Mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, resulting in an altered cell membrane permeability. Antifungal azole. Mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, resulting in an altered cell membrane permeability. Also inhibits peroxidases, which results in accumulation of peroxide within the cell. Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols. Antimicrobial spectrum: Yeasts and molds. Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols. Antimicrobial spectrum: Yeasts and molds. Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols. Antimicrobial spectrum: Yeasts and molds. Mode of Action: Increases the permeability of the cell membrane of sensitive fungi by binding to sterols. Antimicrobial spectrum: Yeasts and molds. An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane. An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane.

Antifungals

Amphotericin B solution, sterile-filtered, 250 μg/mL in deionized water, cell culture tested Cerulenin, ~95%, from Cephalosporium caerulens Clotrimazole

Dermaseptin from Phyllomedusa sauvagii, ≥97% (HPLC) Econazole nitrate salt

Filipin complex from Streptomyces filipinensis, ≥70% (UV)

Fluconazole, ≥98% (HPLC), solid

F8929-100MG

Itraconazole, ≥98% (TLC)

I6657-100MG

Ketoconazole, ≥98% (TLC)

K1003-100MG K1003-1G M3512-1G M3512-5G M3512-25G N1638-20ML N1638-100ML N3503-5MU N3503-25MU N6261-500KU N6261-5MU N6261-25MU N4014-50MG P0440-20ML 80482-20ML

(±)-Miconazole nitrate salt

Nystatin preparation, suspension, sterile; aseptically processed, cell culture tested Nystatin, activity: ≥4,400 USP units/mg Nystatin, powder, cell culture tested

Nystatin, powder, γ-irradiated, cell culture tested Pimaricin preparation, ~2.5%, aqueous suspension Pimaricin preparation, BioChemika, aqueous suspension 2.5%, sterile, ~90% (N)

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Name Pimaricin, from Streptomyces chattanoogensis, ≥95% (HPLC) Staurosporine from Streptomyces sp., ≥95% (HPLC), solid Staurosporine from Streptomyces sp., for molecular biology, ≥95% (HPLC) Staurosporine solution from Streptomyces sp., Rready Made Solution, 1 mM in DMSO (100 μg/214 μL), 0.2 μm filtered Terbinafine hydrochloride, ≥98% 8

Description An antifungal polyene macrolide that binds specifically to ergosterol and blocks fungal growth. However, unlike nysatin and filipin, pimaricin does not change the permeability of the plasma membrane Partially reverses MDR, sensitizing cells with MDR phenotype to cytotoxic agents. Inhibits Pgp phosphorylation. However, functional significance of Pgp phosphorylation is ill defined. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells. Partially reverses MDR, sensitizing cells with MDR phenotype to cytotoxic agents. Inhibits Pgp phosphorylation. However, functional significance of Pgp phosphorylation is ill defined. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells. Potent cell-permeable inhibitor of protein kinase C. Induces apoptosis in Jurkat cells. Mode of Action: Inhibits squalene epoxidase, preventing biosynthesis of ergosterol. Antimicrobial spectrum: Antifungal and antimycotic. Fungicidal against dermatopytes and some yeasts; fungistatic against Candida albicans. -

Cat. No. P9703-25MG P9703-50MG P9703-100MG S4400-.1MG S4400-.5MG S4400-1MG S5921-.1MG S5921-.5MG S5921-1MG S6942-200UL

Antifungals

T8826-100MG T8826-250MG Z2625-250MG Z2625-1G Z2625-5G

Zomepirac sodium salt

Inhibits β-(1→3)Glucan Synthesis
Name Aculeacin A, from Aspergillus aculeatus, ≥95% (HPLC) Azaserine, ≥98% (TLC) Description Aculeacin A, an amphophilic antibiotic, inhibits the biosynthesis of β−glucan by selective blockage of β(1→3) glucan synthase. Azaserine is an antibiotic and antifungal; it may also act as a tumor inducer. It is a structural analog of glutamine and competes with glutamine in binding to enzymes involved in purine biosynthesis. Azaserine inhibits purine biosynthesis by covalently reacting with cysteine residues in the enzyme active sites, such as in formylglycinamide ribonucleotide amidotransferase and PRPP amidotransferase. Azaserine can induce DNA damage via the formation of carboxymethylated bases and O6-methylguanine. Secretion of exo-1,3β-glucanase and germ-tube formation of Candida albicans were inhibited by azaserine. Cat. No. A7603-1MG A4142-50MG A4142-250MG

Chitin Synthesis Inhibitors
Name Cycloheximide, BioChemika, ≥93.0% (HPLC) Description Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors. Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors. Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors. Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors. Nucleoside peptide antibiotic; it inhibits the biosynthesis of chitin in cell walls due to its structural resemblance to UDP-N-acetylglucosamine. Nikkomycin Z has potent antifungal, insecticidal and acaridicial activity. Cat. No. 01810-1G 01810-5G

Cycloheximide, from microbial, ≥94% (TLC)

C7698-1G C7698-5G

Cycloheximide, Biotechnology Performance Certified

C1988-1G C1988-5G

Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, 0.2 μm filtered

C4859-1ML

Nikkomycin Z from Streptomyces tendae, ≥90% (HPLC)

N8028-5MG

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Interferes with DNA, RNA, or Protein Synthesis
Name Cordycepin, from Cordyceps militaris Description Converted to cordycepin 5′-triphosphate. It is incorporated into nucleic acid by poly(A) polymerase, but because it lacks a 3′-hydroxyl group, it causes chain termination. It can be used for 3′-end labeling of RNA. Nucleoside analog that has antifungal activities. 5-FC is deaminated by cytosine deaminase to product 5-fluorouracil, resulting in RNA miscoding. 5-Fluorocytosine inhibits DNA and RNA synthesis and interferes with ribosomal protein synthesis. RNA synthesis inhibitor that acts as a fungicide against Trichophyton mentagrophytes, Myrothecium verrucaria, and Trichoderma viride. The antifungal mechanism of action is not clear but appears to be structurally related. Mode of Action: Blocks polypeptide synthesis and inhibits elongation. For use in the selection and maintenance of prokaryotic and eukaryotic cells. Cat. No. C3394-10MG C3394-25MG C3394-100MG F7129-1G F7129-5G H6878-25G H6878-100G H6878-500G H3274-50MG H3274-100MG H3274-5X100MG H3274-250MG H3274-1G H7772-50MG H7772-100MG H7772-250MG H7772-1G H0654-250MG H0654-500MG H0654-1G H5527-250MG H5527-500MG H5527-1G K4013-10G P9564-5MG P9564-25MG P9564-100MG S1442-5MG

5-Fluorocytosine

8-Hydroxyquinoline, crystalline

Antifungals

Hygromycin B from Streptomyces hygroscopicus, powder, cell culture tested, insect cell culture tested

Hygromycin B from Streptomyces hygroscopicus, lyophilized powder

Mode of Action: Blocks polypeptide synthesis and inhibits elongation. For use in the selection and maintenance of prokaryotic and eukaryotic cells.

Hygromycin B solution from Streptomyces hygroscopicus, ≥60% (HPAE), 45-60 mg/mL in H2O Hygromycin B solution from Streptomyces hygroscopicus, ≥60% (HPAE), 45-60 mg/mL in H2O, γ-irradiated Kasugamycin hydrochloride from Streptomyces kasugaensis, ≥90% (HPLC) Phleomycin from Streptomyces verticillus, powder Sordarin sodium salt, from Sordaria araneosa, ≥98% (HPLC), solid

Antibacterial and antifungal. Mode of action: Inhibition of protein synthesis, by inducing the misreading of the m-RNA template in prokaryotes and eukaryotes. It selectively penetrates cells that have been rendered permeable by virus infection. Antibacterial and antifungal. Mode of action: Inhibition of protein synthesis, by inducing the misreading of the m-RNA template in prokaryotes and eukaryotes. It selectively penetrates cells that have been rendered permeable by virus infection. Antifungal aminoglycoside. Mode of action: Inhibits protein synthesis and binding of aminoacyl-SRNA to the ribosomes in fungi. Phleomycin is a structurally related form of the antibiotic, bleomycin. Phleomycin blocks S-phase entry in the cell cycle. While phleomycin can damage DNA, like bleomycin, it is not used as an anticancer agent, but rather as a selection agent. The RAD6 DNA repair gene is essential for phleomycin resistance in mutant yeast. Sordarin is an antifungal metabolite possessing a tetracyclic diterpene glycoside structure. It is a highly potent inhibitor of eukaryotic protein synthesis with selectivity for the fungal translation machinery. The elongation factor eEF-2 is the molecular target for sordarin. It blocks ribosomal translocation by stabilizing the EF2-ribosome complex in a manner similar to that of fusidic acid in the bacterial system. Additional cellular components (including rpP0, which is an essential protein of the ribosomal large subunit stalk) are involved in its mechanism of action. Sordarin inhibits in vitro translation in the pathogenic fungi C. albicans, C. glabrata, and C. neoformans. In addition to its therapeutic potential, sordarin is a useful tool for the analysis of protein translation events. Thiolutin is a sulfur-containing antibiotic, which is a potent inhibitor of bacterial and yeast RNA polymerases. It was found to inhibit in vitro RNA synthesis directed by all three yeast RNA polymerases (I, II, and III). Thiolutin is also an inhibitor of mannan and glucan formation in Saccharomyces cerevisiae and used for the analysis of mRNA stability. Studies have shown that thiolutin inhibits adhesion of human umbilical vein endothelial cells (HUVECs) to vitronectin and thus suppresses tumor cell-induced angiogenesis in vivo. Toxic adenosine analog with antiviral, antitrypanosomal, and antifungal functions. Mode of action: Inhibits multiple metabolic processes, including RNA processing, nucleic acid synthesis, protein synthesis, and methylation of tRNA through intracellular incorporation into nucleic acids. Tubercidin acts as a plant antifungal, inhibits mammalian SAH hydrolase (SAHH), and blocks purine biosynthesis in Candida famata.

Thiolutin, from Streptomyces luteosporeus, ≥95% (HPLC)

T3450-1MG

Tubercidin, from Streptomyces tubercidicus, ~95%

T0642-10MG T0642-50MG T0642-250MG

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Additional Antifungal Compounds
Name Amiodarone hydrochloride, ≥98% Description Non-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death. Antibiotic isolated from Streptomyces griseolus that inhibits protein synthesis. Acts by inhibiting peptidyl transferase activity in eukaryote ribosomes. Reported to induce apoptosis in a variety of cells including promyelocytic leukemia cells, Jurkat cells, ventricular myocytes, and colon adenocarcinoma cells. Initiates intracellular signals and immediate early gene induction. Selective signaling agonist. Potent Jun-NH2 terminal kinase (JNK) agonist. Activates mitogen-activated protein (MAP) kinases (JNK/SAPK and p38/RK). Antiprotozoal agent. A specific inhibitor of vacuolar type H+-ATPase (V-ATPase) in animal cells, plant cells and microorganisms. Antibacterial peptide originally identified in moths (Hyalophora cecropia) and later in pig intestine. Antifungal. Mode of action: Disrupts the mitotic spindle structure and inhibits nuclear division. Induces apoptosis in human tumor cell lines. Irgasan is a broad spectrum antimicrobial agent. It is an inhibitor of the enoyl-ACP (acyl-carrier protein) reductase component of type II fatty acid synthase (FAS-II) in bacteria and Plasmodium. It also inhibits mammalian fatty acid synthase (FASN), and may have anticarcinogenic activity. Iturin A exhibits strong antifungal activity against pathogenic yeast and fungi. It interacts with the cytoplasmic membrane of the target cell forming ion conducting pores and its mode of action could be attributed to its interaction with sterols and phospholipids. The compound causes the release of exo-vesicles from human erythrocytes. Leptomycin B is an unsaturated, branched-chain fatty acid, and is an important tool in the study of nuclear export. It is a specific inhibitor of proteins containing nuclear export signal. It inhibits nucleo-cytoplasmic translocation of molecules such as the HIV-1 Rev protein and Rev-dependent export of mRNA. The addition of very small amounts to fibroblasts causes accumulation of MEK in the nucleus. Other proteins that are influenced by leptomycin B are actin, c-Abl, cyclin B1, MDM2/p53, IκB, MPF, and PKA. The suggested inhibition mechanism involves the direct binding of leptomycin B to CRM1, which blocks the binding of CRM1 to proteins containing the nuclear export signal, via the interaction with cysteine residue in CRM1 control conserved region. Bioactive plant component with antifungal, antibacterial and antioxidant effects. Magnolol also demonstrates anti-inflammatory activity by interferring with NF-κB signaling. Antifungal effective against Candida albicans. Candida species transformed with the gene encoding nourseothricin acetyltransferase (CaNAT1) were resistant to nourseothricin. Macrolide antibiotic; inhibits mitochondrial ATPase and phosphoryl group transfer. Cat. No. A8423-1G A8423-5G A8423-10G A9789-5MG A9789-25MG A9789-100MG

Anisomycin from Streptomyces griseolus, ~97% (TLC), solid

Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC) Cecropin A, ≥97% (HPLC), powder Griseofulvin, from Penicillium griseofulvum, 97.0-102.0% Irgasan, BioChemika, ≥97.0% (HPLC)

B1793-2UG B1793-10UG C6830-.1MG C6830-.5MG G4753-5G G4753-25G G4753-50G 72779-5G-F 72779-25G-F I1774-1MG I1774-5MG

Antifungals

Iturin A from Bacillus subtilis, ≥90% (HPLC)

Leptomycin B from Streptomyces sp., 5 μg/mL in methanol: water (7:3), ≥95% (HPLC)

L2913-.5UG L2913-2X.5UG L2913-5X.5UG L2913-10X.5UG

Magnolol, ≥95% (HPLC), from plant 8 Nourseothricin sulfate, BioChemika, ≥85% (HPLC) Oligomycin from Streptomyces diastatochromogenes, ~65% oligomycin A basis (Composition given on label), ≥90% total oligomycins basis (HPLC) Rapamycin from Streptomyces hygroscopicus, ≥95% (HPLC), powder

M3445-10MG 74667-10MG O4876-5MG O4876-25MG O4876-100MG O4876-250MG R0395-1MG

Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1. Antibiotic and antifungal from Stigmatella aurantiaca. Inhibits electron transport. Acts at the Qo center of the bc1 complex, binds to the heme b1 domain of cytochrome b as well as to the iron-sulfur protein. Used in studies on hydroubiquinone-cytochrome c2 oxidoreductase. Lipopeptide antibiotic; powerful biosurfactant causes lysis of erythrocytes and bacteria; also a clotting inhibitor. Antibacterial and antifungal. Blocks the formation of protein N-glycosidic linkages by inhibiting the transfer of N-acetylglucosamine 1-phosphate to dolichol monophosphate. Inhibits bacterial and eukaryote N-acetylglucosamine transferases and prevents formation of N-acetylglucosamine lipid intermediates.

Stigmatellin, BioChemika, ≥95.0% (HPLC)

85865-1MG 85865-10MG S3523-10MG S3523-50MG T7765-1MG T7765-5MG T7765-10MG T7765-50MG

Surfactin, from Bacillus subtilis, ≥98% Tunicamycin from Streptomyces sp.

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New Antibiotics
Adefovir dipivoxil
9-(2[bis(Pivaloyloxymethoxy)phosphorylmethoxy]ethyl)adenine [142340-99-6] C20H32N5O8P FW 501.47
Antiviral acyclic nucleoside phosphonate (ANP) analog.
store at: −20°C A9730-50MG A9730-100MG 50 mg 100 mg 8 8

Cytochalasin B from Drechslera dematioidea
Phomin [14930-96-2] C29H37NO5 FW 479.61
CH2 H3C H HN O O O OH H

8

CH3

OH

Artesunate New Antibiotics
C19H28O8 FW 384.42

One of a group of fungal metabolites that interfere with a wide variety of cellular movements. Useful tool for characterizing some of the polymerization properties of actin,† and in studies on cytokinesis.1 Probe for the two hexose-transport systems in rat L6 myoblasts.2
Lit cited: 1. S. Eperon, J. Protozool. 33, 43 (1986); 2. S.R.Chen, Biochem. J. 251, 3 (1988);

Artesunate is a semisynthetic derivative of artemisinin used to treat malaria.1 It has also been shown to effective against other parasites such as liver flukes.2 Artesunate also demonstrates cytotoxic action against cancer cell lines of different tumor types.3
Lit cited: 1. Prince, R.N., Expert Opin. Investig. Drugs 9, 1815-1827 (2000); 2. Keiser, J., et. al., Antimicrob. Agents Chemother. 57, 1139-1145 (2006); 3. Efferth, T., et. al., Mol. Pharmacol. 64, 382-394 (2003);

 Ready Made Solution, 10 mg/mL in DMSO, 0.2 μm filtered
Inhibits actin polymerization; inhibits glucose transport.
ship: wet ice store at: −20°C C2743-200UL 200 μL 8
H2C H3C H HN O H3C O O HO OH H H CH3 O CH3

 from Artemisia annua
store at: Room temp A3731-100MG A3731-500MG 100 mg 500 mg 8
O HO H H HO O CH3

Cytochalasin D
Zygosporin A [22144-77-0] C30H37NO6 FW 507.62

Brefeldin A
γ,4-Dihydroxy-2-(6-hydroxy-1-heptenyl)-4-cyclopentanecrotonic acid λ-lactone; BFA; Cyanein; Ascotoxin; Decumbin [20350-15-6] C16H24O4 FW 280.36

Potent inhibitor of actin polymerization; disrupts actin microfilaments; activates the p53-dependent pathways; inhibits smooth muscle contraction; inhibits insulin-stimulated glucose transport.

Disrupts the structure and function of the Golgi apparatus; activator of the sphingomyelin cycle.

 Ready Made Solution, from Zygosporium masonii, 5 mg/mL in DMSO, 0.2 μm filtered
ship: wet ice store at: −20°C C2618-200UL 200 μL 8

 from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO, 0.2 μm filtered
ship: wet ice store at: 2-8°C B5936-200UL 200 μL 8

17-Dimethylaminoethylamino-17-demethoxygeldanamycin
17-DMAG C32H48N4O8 FW 616.75

Cefdinir

[6R-[6α-7beta(Z)]]-7-[[(2-Amino-4-thiazolyl)(hydroxyimino)acetyl]amino]3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; BMY-28488; FK-482; syn-7-[2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid [91832-40-5] C14H13N5O5S2 FW 395.41
An advanced-generation, cephalosporin antibiotic. Used for its excellent and well balanced antibacterial activities against gram-positive and gram-negative bacteria. solid solubility dilute HCl .............................................................................slightly soluble mp..................................................................................................... 170 °C
store at: Room temp C7118-1G C7118-5G 1g 5g 8

17-DMAG is a more potent water soluble analog of geldanamycin. Inhibits cancer growth and promotes apoptosis in multiple cell lines. 17-DMAG is a more potent antitumor agent than 17-AAG. solubility DMSO ...................................................................................... >25 mg/mL ethanol ..................................................................................... ~10 mg/mL
store at: −20°C D5193-1MG 1 mg 8

Pediocin from Pediococcus acidilactici
[133108-87-9]

Clarithromycin
[81103-11-9] C38H69NO13 FW 747.95

Pediocins are class IIa bacteriocins that are produced by Pediococcus sp.1 They are cationic peptides that show strong activity against pathogenic bacteria such as Listeria monocytogenes, Clostridicum perfringes, Enterococcus faecalis, and Staphylococcus aureus.2 This antimicrobial action of pediocins is based on interaction with the cytoplasmic membrane, resulting in pore formation and cell death.
Lit cited: 1. Bauer, R. and Dicks, L.M., Mode of action of lipid II-targeting lantibiotics. Int. J. Food Microbiol. 101, 201-16 (2005); 2. Bhunia, A.K., et al., Purification, characterization and antimicrobial spectrum of a bacteriocin produced by Pediococcus acidilactici. J. Appl. Bacteriol. 65, 261-8 (1988);

Clarithromycin is a macrolide antibiotic. It prevents bacterial growth by interfering with protein synthesis. Clarithromycin is an acid-stable version of erythromycin and is particularly effective against gram-negative bacteria.1 It has a short half-life2, however its metabolite, 14-hydroxy clarithromycin is nearly twice as active as clarithromycin against certain bacteria.3
Lit cited: 1. Hardy, D.J. et al., Diagn. Microbiol. Infect. Dis. 15, 39-53 (1992); 2. Langtry, H.D., and Brogden, R.N., Drugs 53, 973-1004 (1997); 3. Hardy, D.J, et al., Antimicrob. Agents Chemother. 32, 1710-1719 (1988);

 ≥95% (HPLC), buffered aqueous solution
concentration ............................ 0.1 mg/mL in 0.1 M sodium acetate pH 5.0
ship: dry ice store at: −20°C P0098-50UG 50 μg

 ≥95% (HPLC)
C9742-100MG C9742-250MG C9742-1G 100 mg 250 mg 1g

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Pefloxacin mesylate dihydrate
Pefloxacinium methanesulfonate dihydrate; Pefloxacine monomethanesulfonate dihydrate; 3-Quinolinecarboxylic acid, 1-ethyl6-fluoro-1,4-dihydro-7-(4-methyl-1piperazinyl)-4-oxo-, monomethanesulfonate, dihydrate C17H20FN3O3 • CH4O3S • 2H2O FW 465.49
O F N H3C N H3C N O

8
O OH • HO S CH3 O • 2H2O

Rapamycin

8

23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine solution C51H79NO13 FW 914.17
Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1.

New Antibiotics

Pefloxacin is a synthetic fluoroquinolone that functions an antibacterial agent. It is an analog of norfloxacin. Mode of Action: Pefloxacin prevents bacterial DNA replication by inhibiting DNA gyrase. Antimicrobial spectrum: Pefloxacin is highly active against Staphylococcus aureus, E. coli, other enterobacteria, and Pseudomonas aeruginosa.1 Active against gram-positive bacteria and excellent activity against gram-negative bacteria.2
Lit cited: 1. Jones, B.M. et al., Activity of pefloxacin and thirteen other antimicrobial agents in vitro against isolates from hospital and genitourinary infections J. Antimicrob. Chemother. 17, 739-746 (1986); 2. Debbia, E. et al., In vitro activity of pefloxacin against gram-negative and gram-positive bacteria in comparison with other antibiotics. Chemotherapia 6, 319-326 (1987); store at: 2-8°C P0106-10G P0106-50G 10 g 50 g 8

 Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM),  from Streptomyces hygroscopicus
≥95% (HPLC) 0.2 μm filtered
store at: −20°C R8781-200UL 200 μL

Penicillic acid
3-Methoxy-5-methyl-4-oxo-2,5-hexadienoic acid; PA [90-65-3] C8H10O4 FW 170.16

A Perfect Fit!

Penicillic acid is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium species. It induces single and double strand DNA breaks. Penicillic acid irreversibly inhibits GDP-mannose dehydrogenase (DMG), an alginate synthesis enzyme. It also inhibits muscle aldose dehydrogenase, alcohol dehydrogenase, and lactate dehydrogenase.

 ≥98% (HPLC)
solubility H2O ...........................................................................................≤10 mg/mL DMSO ...................................................................................... >10 mg/mL
store at: 2-8°C P0063-10MG P0063-50MG 10 mg 50 mg 8
O OH O OH OH CH3O O O OH O O CH3 O NH2

Pirarubicin
THP [72496-41-4] C32H37NO12 FW 627.64

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Anthracycline antibiotic that is an analog of doxorubicin. Antineoplastic. Pirarubicin is transported into cells vial a sodium-dependent nucleoside transporter.1,2
Lit cited: 1. Nagai, K., et al., Pirarubicin is taken up by a uridine-transportable sodiumdependent concentrative nucleoside transporter in Ehrlich ascites carcinoma cells. Cancer Chemother. Pharmacol. 51, 512-8 (2003); 2. Nagai, K., et al., Uptake of the anthracycline pirarubicin into mouse M5076 ovarian sarcoma cells via a sodium-dependent nucleoside transport system. Cancer Chemother. Pharmacol. 55, 222-30 (2005);

Life Science Innovations—new and emerging technologies, put forth in a fresh, unique way, that applies to your area of study BioFiles—tailored for the life science researcher, aligns our vast array of products within a relevant research topic

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 ≥95% (HPLC)
ship: wet ice store at: 2-8°C P8624-10MG P8624-25MG 10 mg 25 mg

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Rifaximin
Rifacol; 4-Deoxy-4′-methylpyrido[1′,2′-1,2] imidazo[5,4-c]rifamycin SV [80621-81-4] C43H51N3O11 FW 785.88
O O OH

8

O OH O O O O N N CH3 OH OH NH

Starting a new lab?

Rifaximin is a semisynthetic analog of rifamycin with poor absorptivity. Mode of action: Inhibition of RNA synthesis. Antimicrobial spectrum: Aerobic and anaerobic Gram-positive and Gramnegative bacteria. Active against species of Staphylococcus, Streptococcus and Enterococcus; less active against species of Enterobacteriaceae.1
Lit cited: 1. Gillis, J.C. and Brogden, R.N., Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 49, 467-84 (1995); store at: 2-8°C R9904-1G R9904-5G 1g 5g 8

New Antibiotics

Spiramycin adipate
Spiramycin hexanedioate
Macrolide antibiotic Mode of action: Interferes with protein synthesis Antimicrobial spectrum: mainly Gram-positive bacteria
store at: 2-8°C S3072-1G S3072-5G

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Sulfadoxin
[2447-57-6] C12H14N4O4S FW 310.33
H3CO H3CO N HN O O S N

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NH2

 ≥95% (TLC)
Sulfadoxine is a sulfonamide antibacterial. It inhibits dihydropteroate synthase (DHPS), an enzyme that transforms 4-aminobenzoic acid (PABA) in the synthesis of dihydropteroic acid. This enzyme is also a component of the folate metabolic pathway and is upstream of dihydrofolate reductase (DHFR). Sulfadoxine has been used clinically in combination with pyrimethamine for malaria treatment.
S7821-10G S7821-25G 10 g 25 g 8
CH3 H N H • HCl CH3 CH3 CH3

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Terbinafine hydrochloride
trans-N-(6,6-Dimethyl-2-hepten-4-ylyl)-Nmethyl-1-naphthylmethylamine hydrochloride [78628-80-5] C21H25N · HCl FW 327.89

Mode of Action: Inhibits squalene epoxidase, preventing biosynthesis of ergosterol. Antimicrobial spectrum: Antifungal and antimycotic. Fungicidal against dermatopytes and some yeasts; fungistatic against Candida albicans. Allylamine derivative.

 ≥98%
T8826-100MG T8826-250MG 100 mg 250 mg

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Ready Made Solutions
Sigma® Life Science Antibiotic Ready Made Solutions arrive at your laboratory as sterile-filtered, ready to use formulations. Ready Made antibiotic solutions minimize your exposure to potentially harmful powders, reducing your risk as well as saving your time. All Ready Made Solutions are 0.2 μm filtered for extended shelf life and prevention of bacterial contamination. As with all Sigma Life Science products, strict quality control measures apply to each Ready Made Solution. For more information on Ready Made Solutions, please visit sigma.com/readymade
Name Ampicillin Concentration 100 mg/mL Source microbial Description A β-lactam antibiotic with an amino group side chain attached to the penicillin structure. Penicillin derivative that inhibits bacterial cell-wall synthesis (peptidoglycan cross-linking) by inactivating transpeptidases on the inner surface of the bacterial cell membrane. Bactericidal only to growing Escherichia coli. Mode of resistance: Cleavage of β-lactam ring of ampicillin by β-lactamase. Antimicrobial spectrum: Gram-negative and Gram-positive bacteria. Disrupts the structure and function of the Golgi apparatus; activator of the sphingomyelin cycle. The antibiotic carbenicillin, an ampicillin analog, is a commonly used selection agent that binds and inhibits enzymes involved in the synthesis of the bacterial cell wall. It is active against most isolates of Pseudomonas aerogenosa and certain indole-positive Proteus strains that are resistant to ampicillin. The gene conferring resistance to ampicillin and its analogs, ampr, codes for the enzyme β-lactamase. Carbenicillin is less sensitive to β-lactamase than ampicillin. In addition it has a superior stability at low pH. Experiments have shown that the use of carbenicillin in place of ampicillin helps prevent overgrowth of satellite colonies. Effective concentration: 50 to 100 μg/ml. Cycloheximide (CHX) is an antibiotic produced by S. griseus. Its main biological activity is translation inhibition in eukaryotes resulting in cell growth arrest and cell death. CHX is widely used for selection of CHX-resistant strains of yeast and fungi, controlled inhibition of protein synthesis for detection of short-lived proteins and super-induction of protein expression, and apoptosis induction or facilitation of apoptosis induction by death receptors. One of a group of fungal metabolites that interfere with a wide variety of cellular movements. Useful tool for characterizing some of the polymerization properties of actin,† and in studies on cytokinesis. Probe for the two hexose-transport systems in rat L6 myoblasts. Inhibits actin polymerization; inhibits glucose transport. Potent inhibitor of actin polymerization; disrupts actin microfilaments; activates the p53-dependent pathways; inhibits smooth muscle contraction; inhibits insulin-stimulated glucose transport. Ca2+ ionophore that is more effective than A23187 as a mobile ion carrier for Ca2+. Puromycin inhibits the growth of a wide range of eukaryotic and prokaryotic cells by interfering with protein synthesis. It allows the selection of cells expressing the pac gene. Cat. No. A5354-10ML

Ready Made Solutions

Brefeldin A 8 Carbenicillin

10 mg/mL in DMSO 100 mg/mL in ethanol/water

Penicillium brefeldianum -

B5936-200UL C1613-1ML

Cycloheximide solution

100 mg/mL in DMSO

microbial

C4859-1ML

Cytochalasin B from Drechslera dematioidea 8

10 mg/mL in DMSO

Drechslera dematioidea

C2743-200UL

Cytochalasin D 8

5 mg/mL in DMSO

Zygosporium masonii Streptomyces conglobatus Streptomyces alboniger

C2618-200UL

Ionomycin calcium salt Puromycin dihydrochloride

1 mM in DMSO 10 mg/mL in H2O

I3909-1ML P9620-10ML

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Name Rapamycin 8

Concentration 2.5 mg/mL in DMSO (2.74 mM)

Source Streptomyces hygroscopicus

Description Rapamycin is a macrocyclic triene antibiotic possessing potent immunosuppressant and anticancer activity. It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). mTOR is a member of the phosphoinositide kinase-related kinase (PIKK) family that enhances cellular proliferation via the phosphoinositol 3-kinase/ Akt signaling pathway. Inhibition of this pathway by rapamycin blocks downstream elements that result in cell cycle arrest in G1. The effectors of mTOR action include 4EBP1 and S6K1. Mode of Action: Inhibits protein synthesis (elongation) by interfering with peptidyl tRNA translocation. Antimicrobial spectrum: Gram-negative and Gram-positive bacteria (Gonnococcus only). Mode of Resistance: Mutation in rpsE (the gene for ribosomal protein S5) prevents binding of spectinomycin. Broad spectrum antibiotic produced by the soil bacterium Streptomyces spectabilis. Spectinomycin inhibits protein synthesis (elongation) by binding to the bacterial 30S ribosomal subunit and interfering with peptidyl tRNA translocation. Resistance to spectinomycin is conferred by aminoglycoside3′-adenyltransferase gene (aadA). Spectinomycin is used as a selection marker in plant related transformation systems. Spectinomycin is also used for amplification of low copy number plasmid carrying replicons as Col E1, pMB1 (pBR322 and its derivatives), and p15A/rep (pACYC and its derivatives). The replication of these plasmids relies on long-lived enzymes supplied by the host. Addition of spectinomycin to the plasmid containing cells inhibits replication of the host, while the plasmids continue to replicate for 10-15 hours. The copy number of the plasmid can increase 100-fold, from 20-30 copies to 3000 copies as in the case of ColE1. Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells. Potent cell-permeable inhibitor of protein kinase C. Induces apoptosis in Jurkat cells. Trichostatin A is a Streptomyces metabolite, which specifically inhibits mammalian histone deacetylase. K+-selective ionophore which uncouples oxidative phosphorylation.

Cat. No. R8781-200UL

Spectinomycin

100 mg/mL in DMSO/H2O, 1:1

Streptomyces sp.

S0692-1ML

Ready Made Solutions

Staurosporine solution from Streptomyces sp.

1 mM in DMSO (100 μg/214 μL)

Streptomyces sp.

S6942-200UL

Trichostatin A 8 Valinomycin

5 mM in DMSO (0.2 μm-filtered) ~ 1 mg/mL in DMSO

Streptomyces sp. Streptomyces sp.

T1952-200UL V3639-5ML

Sigma is Cell Culture

The 3rd edition of the Sigma Cell Culture Manual is a hybrid reference and product guide designed to be a foundation for your discovery efforts.
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Extensive cell culture technical information and formulas Our most popular cell culture products and equipment Invaluable tool to help advance your research goals

Order your copy of the 2008–2009 Cell Culture Manual by visiting sigma.com/ccmanual
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Antibiotic Selector
The Antibiotic Selector enables researchers to spend more time on their research discoveries and less time seeking established antibiotic information. Link to nearly 200 antibiotics for contamination prevention, genetic marker selection and cell biology studies. Access application, activity spectrum, and usage data derived from a combination of hands on experience, peer-reviewed literature, and Sigma quality control analysis.
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Quickly find the best antibiotic for your research. Detailed application and usage information. Link to easy online ordering.

For more information, visit sigma.com/antibiotics

The following tutorial provides instructions on how to:

Search, browse and filter for an antibiotic that meets your research requirements Access solvent, solution storage and working concentration recommendations for each antibiotic Link to current pricing, availability and easy, online ordering

SearchIf you already know your antibiotic of interest, search the name then select it from the results to access the detailed usage and application information. Close the window to return to the main antibiotic selector window. Start a new search by clicking the red “New Search” button.

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Application and usage information

BrowseTo browse antibiotics by application, select one of the following from the Application menu: cell culture, plant cell culture, selection agent, antineoplastic agent. To browse antibiotics by activity spectrum, select one of the following from the Activity Spectrum menu: Gram +, Gram -, Mycobacteria, Yeast, Molds, Mycoplasmas and Viruses. You can further refine your results by first browsing the antibiotics by application and then filtering the results by a specific activity spectrum or first browsing by activity spectrum and then filtering the results by application. Click on your antibiotic of interest from the list to access the detailed usage information. Once you have completed a search, be sure to start a new search by clicking the red “New Search” button before starting a new search or browsing by application or activity spectrum.
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We expect the Antibiotic Selector to be a beneficial tool for you and your colleagues. To access the Antibiotic Selector, please visit sigma.com/antibiotics

The Bioactive Nutrient Explorer
Your connection to plant defense compounds

Designed to help you locate the chemicals and kits needed to support your antimicrobialrelated phytochemical research, the Bioactive Nutrient Explorer is an Internet-based tool that identifies the compounds found in a specific plant and arranges them by chemical family and class. You can also search for compounds having a similar chemical structure or for plants containing a specific compound. When you’ve found the product you need, a simple mouse click links you to our easy online ordering system.

Link Antibacterial, Antifungal, and Antiviral Actions to Specific Plants Review AntimicrobialRelated Chemical Families: Tannins, Terpenoids, Phenols, Flavones, and Alkaloids. Locate Defense Phytochemicals Found in Specific Plants

Bioactive Nutrient Explorer Helping Scientists Connect Bioactives to Botanicals Visit sigma-aldrich.com/nutrition
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