Mary K. Campbell Shawn O.

Farrell
http://academic.cengage.com/chemistry/campbell

Chapter Three Amino Acids and Peptides

Jong Wha Lee, Ph.D. June 2011

3.1 Amino Acids Exist in a 3-D World 3.2 Individual Amino Acids: Their Structures and Propertie 3.3 Amino Acids Can Act as Both Acids and Bases 3.4 The Peptide Bonds 3.5 Small Peptides with Physiological Activity

3.1 Amino Acids Exist in a 3-D World
• Amino acid: a compound that contains both an amino group and a carboxyl group

• α-Amino acid has an amino group attached to the carbon adjacent to the carboxyl group • α-carbon also bound to side chain group, R • R gives identity to amino acid  The nature of the side chains is the basis of the differences among amino acids.

Ionic forms that predominate at pH 7

Stereochemistry of Amino Acids
• • • • Except for glycine, amino acids can exist in 2 steroisomers, designated L and D. Based on similarity to glyceraldehdye These 2 stereoisomers are nonsuperimposable mirror images of each other. Chiral vs. achiral The amino acids found in proteins are of the L form, but some D-amino acids occur in nature.

FIGURE 3.2 Stereochemistry of alanine and glyceraldehyde. The amino acids found in proteins have the same chirality as L-glyceraldehyde, which is opposite to that of D-glyceraldehyde.

Summary 3-1. 66 . p.

all protein-derived amino acids have at least one stereocenter (the αcarbon) and are chiral (stereoisomers) • the vast majority of α-amino acids have the Lconfiguration at the α-carbon (Proline is usually D-form) • Side-chain carbons in other amino acids designated with Greek symbols.3. .2 Individual Amino Acids: Their Structures and Properties • With the exception of glycine. starting at α− carbon (β− γ− δ− . and ε− carbon …etc) • Amino acids can be referred to by three-letter or oneletter codes. .

Individual Amino Acids Non-polar (hydrophobic) side chains (Group 1) • Gly • Ala. pyrrolidine. Pro: aliphatic hydrocarbon group • Pro: aliphatic cyclic side group. • Met: Sulfur atom containing aliphatic hydrocarbon group. Leu. aromatic. . Val. amino group secondary amine  imino acid • Phe: aromatic hydrocarbon ring side chain • Trp: Indole ring side chain. Ile.

Amino Acids (cont’d) Polar. uncharged side chains (Group 2) •Ser. Thr: hydroxyl group •Tyr: hydroxyl group bonded to aromatic hydrocarbon group •Cys: thiol group (-SH) •Gln. Asn: amide bonds .

Asp Both have a carboxyl group in side chain Can lose a proton.Amino Acids (cont’d) • Acidic Side Chains (Group 3) • • • • Glu. forming a carboxylate ion These amino acids are negatively charged at neutral pH .

Amino Acids (cont’d) Basic side chains (Group 4) • Side chains are positively charged at pH 7 • Arg: guanidino group • His: imidazole group • Lys: NH3 group is attached to an aliphatic hydrocarbon chain Arginine (Arg. K) . R) Lysine (Lys.

the α-carbon of each is a stereocenter 4. the α-amino group is primary. Isoleucine and threonine contain a second stereocenter 5. For 19 of the 20. and 1-letter codes . 3. for proline. With the exception of glycine. All 20 are α-amino acids 2. it is secondary 3.Amino Acid Summary Important structural features: 1.

Uncommon Amino Acids • Each derived from a common amino acid by a modification • hydroxylysine and hydroxyproline are found only in a few connective tissues such as collagen • thyroxine is found only in the thyroid gland .

Summary 3-2. 73 . p.

carboxyl group (-) and amino group (+) are charged at neutral pH. • In free amino acids. α-amino groups and some side chains have titratable protons. α-carboxyl.3. .3 Amino Acids Can Act as Both Acids and Bases Ionization of Amino Acids • In amino acid.

amino acids without charged groups on side chain exist in neutral solution as zwitterions with no net charge FIGURE 3.Ionization of Amino Acids • Remember. anionic form is at the high-pH . Cationic form is at the low-pH.5 The ionization of amino acids.

pI • pH at which positive and negative charges are the same has no net charge Titration curve of alanine.Titration of Amino Acids • When an amino acid is titrated. • . the titration curve represents the reaction of each functional group with the hydroxide ion Isoelectric pH.

5 The ionization of histidine (an amino acid with a titratable side chain).Ionization of Amino Acids FIGURE 3. .

Titration of histidine with NaOH .

76) • the greater acidity of the amino acid carboxyl group is due to the electron-withdrawing inductive effect of the α-NH3+ group .19.Acidity α-COOH Groups • The average pKa of an α-carboxyl group is 2. which makes them considerably stronger acids than acetic acid (pKa = 4.

47.48) is a considerably stronger base than an aliphatic amine • basicity of the guanidino group is attributed to the large resonance stabilization of the protonated form relative to the neutral form Imidazole Group • The side chain imidazole group of histidine is a heterocyclic aromatic amine .Basicity α-NH3+ groups • The average value of pKa for an α-NH3+ group is 9.76 for a 2° alkylammonium ion Guanidine Group • The side chain of arginine (pKa = 12. compared with a value of 10.

we can calculate the ratio of each acid to its conjugate base as a function of pH • Consider the ionization of an α-COOH α−COOH + H3O pK a = 3 .Ionization vs pH • Given the value of pKa of each functional group.33 α−COO + H3O+ - • writing the acid ionization constant and rearranging terms gives (remember Ch. 2) Ka = [H3 +] [α-COO-] O [α-COOH] or [α-COO-] [α-COOH] = Ka [H3 +] O .

3  x  3 3 3 3 ­3 . and has a net charge of -1 • we can repeat this calculation at any pH and determine the ratio of [α-COO-] to [α-COOH] and the net charge on the α-carboxyl at that pH .0.Ionization vs pH (cont’d) • substituting the value of Ka (1 x 10-2) for the hydrogen ion concentration at pH 7. the α-carboxyl group is virtually 100% in the ionized or conjugate base form.0 x 10-7) gives [α-COO-] [α-COOH] = Ka [H3 +] O = 3 3 3 ­3 .3  x  3 = 3   x  3 .3333 • at pH 7.0 (1.

assume a value 10.0 for pKa + α−NH3 + H3O pK a = 33 .33 α−NH3 + H3O+ • writing the acid ionization constant and rearranging gives [α-NH3] Ka [α-NH3+] = [H3O+] . for this calculation.Ionization vs pH (cont’d) • We can also calculate the ratio of acid to conjugate base for an α-NH3+ group.

3  x  3 = = = 3   x  ­3 . the ratio of α-NH2 to α-NH3 + is approximately 1 to 1000 • at this pH.Ionization vs pH • substituting values for Ka of an α-NH3+ group and the hydrogen ion concentration at pH 7.3333 + + [H3O ] [α-NH3 ] 3 3 3 ­3 .0. an α-amino group is 99.9% in the acid or protonated form and has a charge of +1 .0 gives Ka 3 3 3 ­33 .3  x  3 [α-NH3] • at pH 7.

Henderson-Hasselbalch Equation • We have calculated the ratio of acid to conjugate base for an α-carboxyl group and an α-amino group at pH 7.0 • We can do this for any weak acid and its conjugate base at any pH using the Henderson-Hasselbalch equation pH = pK a  + log [conjugate base] [weak acid] .

22 .Isoelectric pH • Isoelectric pH. for example.33 3 • Isoelectric pH values for the 20 protein-derived amino acids can be calculated .33 . falls midway between the pKa values for the carboxyl and amino groups pI =  3(pKa α−COOH + pKa α−NH3+) 3 =  3 (2   +  3 ) = 3 . pI: the pH at which the majority of molecules of a compound in solution have no net charge • the pI for glycine.

and cellulose acetate as solid supports • in paper electrophoresis. nucleic acids • Isoelectric pH or isoelectric point (pI) . starch. a paper strip saturated with an aqueous buffer of predetermined pH serves as a bridge between two electrode vessels • Protein. certain plastics.Electrophoresis • Electrophoresis: the process of separating compounds in an electric field on the basis of their electric charge • electrophoresis of amino acids can be carried out using paper. agar.

p. 76 .Summary 3-3.

• Peptide bond: the special name given to the amide bond between the αcarboxyl group of one amino acid and the αamino group of another amino acid .3.4 The Peptide Bonds • Individual amino acids can be linked by forming covalent bonds.

3-9.9 A small peptide showing the direction of the peptide chain (N-terminal to C-terminal). Fig. p.FIGURE 3. 78 .

.10 The resonance structures of the peptide bond lead to a planar group. a peptide bond is most accurately represented as a hybrid of 2 contributing structures (resonance structures) • The hybrid has considerable C-N double bond character  rotation about the peptide bond is restricted FIGURE 3. (b) The planar peptide group. (a) Resonance structures of the peptide group.Geometry of Peptide Bond • The 4 atoms of a peptide bond and the 2 α-carbons joined to it lie in a plane with bond angles of 120° about C and N • To account for this geometry.

Peptides • peptide: the name given to a short polymer of amino peptide acids joined by peptide bonds. they are classified by the number of amino acids in the chain • dipeptide: a molecule containing 2 amino acids joined dipeptide by a peptide bond • tripeptide: a molecule containing 3 amino acids tripeptide joined by peptide bonds • polypeptide: a macromolecule containing many polypeptide amino acids joined by peptide bonds • protein: a biological macromolecule of molecular protein weight 5.000 g/mol or greater. consisting of one or more polypeptide chains .

78 . p.Summary 3-4.

3.5 Small Peptides with Physiological Activity • Dipeptide: Carnosine in muscle tissue FIGURE 3. .11 Structures of carnosine and its component amino acid ß-alanine.

81 . p. 3-12a.Tripeptide • Glutathione • γ-glutamyl-L-cysteinylglycine • scavenger for oxidizing agents Fig.

p. 81 . 3-12c.Glutathione Fig.

Pentapeptides • Enkephalins in brain • Naturally occurring analgesics (pain relievers) • Different only in the C-terminal amino acids • Leucine enkephalin: Tyr-Gly-Gly-Phe-Leu • Methionine enkephalin: Tyr-Gly-Gly-Phe-Met .

Cyclic Nonapeptides • Cyclic structures • Disulfide bond • Peptide hormones • Posterior pituitary gland • Oxytocin • Target organs: uterus/ mammary glands • Cervix stretches and suckling  Positive feedback  hypothalamus  posterior pituitary gland  Oxytocin… • Vasopressin • Stimulates reabsorption of water by the kidney  antidiuretic effect  blood pressure increases .

gramicidin S.Cyclic Decapeptides • • • • Cyclic structures: peptide bonds Bacillus brevis  Antibiotics D-amino acids L-ornithine: not in proteins.14 Structures of ornithine. and tyrocidine A. . but in a metabolic intermediate FIGURE 3.

Summary 3-5. p. 83 .

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