Chemical Biology as a Research, Achievements and Opportunities

Presenter – Gourav Das, MS student, Dr Dimpy Kalia’s Lab, Chemical Biology lab
Enzymes are specific catalysts

Effect of an enzyme on reducing the activation energy

required to start a reaction where (a) is uncatalysed
and (b) is an enzyme-catalyzed reaction.
Different enzyme classes
• Competitive binding of inhibitors to the active site.
• Inhibitor Competes with the substrate to bind with the active site.
• Competitive inhibitor has a close structural resemblance with the substrate.
• Degree of inhibition depends upon the substrate and inhibitor concentrations.
• Diminishes the reaction rate by reducing the proportion of the enzyme molecules bound to a substrate.
• Example: Many microorganisms, like bacteria, synthesise the vitamin folic acid from PABA
and some sulfa drugs that are structural analogues of PABA act as an enzyme inhibitor
• Inhibition of enzymatic activity by binding inhibitors to the enzyme at a place other than the active site.
• No competition between the substrate and the inhibitor for the binding to the active site.
• No structural resemblance to the substrate.
• Formation of both enzyme-inhibitor complex and enzyme-substrate complexes takes place.
• Examples: Various heavy metal ions (Ag+, Hg2+, Pb2+) inhibit the activity of various enzymes like urease.
• Prof. Waldman and co-workers have shown a small molecule collection based on the ses-quiterpene-dys-idiolide
structural framework isolated from the Caribbean sponge Dysidea ehteria.
• It exhibits inhibitory activity against a phosphatase protein Cdc25A.
• Prof. Schreiber took an indole alkaloid spiro-tryprostatin B as a prototype in a new library study of 3,232 spiro
oxindole molecules.
• Isolated from the saprophyte mould Aspergilliusfumigatus has been found to have antimitotic properties.
• Helps to identify enhancers of growth arrest induced by latrunculin B.
• Shakir and co-workers [71], a small (2,527) library of molecules were developed inspired by the alkaloid galantamine,
a potent AChE inhibitor.
• molecules proficient in perturbing the protein traffic from the endoplasmic reticulum to the plasma membrane through
the Golgi apparatus.
General reaction scheme of LD chemistry
General reaction scheme for the Affinity Gifted Catalysis strategy.
Schematic Representation of the development of the Labelling Reagent
Drug development and protein modification

 In the field of Drug Development, Chemical biology has the potential to design and testing of
various drugs targeted towards various diseases
 Chemical synthesis and its cellular testing depicts quite a marginal diversity in chemical biology
 Various FDA-approved drugs are being synthesis by chemical, biological methods
 Why Chemical biology has many challenges?
 Many chemicals synthesis are needed for studying only one phenomenon in biology
 Absence of acute cellular condition for conservation of many bioconjugates
 Chemical nature gets unpredicted in physiological conditions
 Chemical moiety’s biological function get varies from different isomeric conditions
 Irregularities in mimicking cellular in vitro processes
 Many protein-protein interactions are unpredictable, so their artificial synthesis is quite challenging.
 Future

• Chemical biology demonstrates how reactions and small molecules can be used in a fascinating way to
study biology.
• Show how it analyses the structures and functions of materials produced by chemical or biological means.
• Chemical biology is now capable of and will achieve success in the discovery of new biological
phenomena, expanding our knowledge horizons about living beings, including ourselves
 Thanks to Chemistry club IISER Bhopal for giving me the opportunity.
Thanks to Dr Dimpy Kalia for her support and guidance.
Special thanks to my mentor Shaikh Dastgir for his constant guidance and support.