1. Chapter Three Amino Acids and Peptides

2. 20 amino acids
Titration of amino acids
Peptide bond

3. Amino Acids
Amino acid: a compound that contains both an amino group and a carboxyl group
-Amino acid has an amino group attached to the carbon adjacent to the carboxyl group
-carbon also bound to side chain group, R
R gives identity to amino acid
Two steroisomers of amino acids are designated L- or D-. Based on similarity to glyceraldehdye (Figure 3.2)

6. Individual Amino Acids
• Group A: Nonpolar side chains- Ala, Val, Leu, Ile, Pro. Phe, Trp, Met.
• Ala, Val, Leu, Ile, Pro- contain aliphatic hydrocarbon group. Pro has cyclic structure.
• Phe- hydrocarbon aromatic ring.
• Trp- Indole ring side chain, aromatic.
• Met- Sulfur atom in side chain.

7. Amino Acids (cont’d)
Group B: Neutral Polar side chains- Ser, Thr, Tyr, Cys, Gln, Asn
Ser, Thr- Side chain is polar hydroxyl group
Tyr- hydroxyl group bonded to aromatic hydrocarbon group
Cys- Side chain contains thiol group (-SH)
Gln, Asn- contain amide bonds in side chain

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

9. Amino Acids (cont’d) Group D: Basic side chains: His, Lys, Arg
Side chains are positively charged at pH 7
Arg-side chain is a guanidino group
His-side chain is an imidazole group
Lys-side chain NH3 group is attached to an aliphatic hydrocarbon chain

10. Amino acid summary Important structural features:
All 20 are -amino acids
2. For 19 of the 20, the -amino group is primary; for proline, it is secondary
3. With the exception of glycine, the a-carbon of each is a stereocenter
4. Isoleucine and threonine contain a second stereocenter
5. 3, and 1-letter codes in Table 3.1.

11. Ionization of Amino Acids
• In amino acid, carboxyl group (-) and amino group (+) are charged at neutral pH.
• In free amino acids -carboxyl, and a-amino groups have titratable protons. Some side chains do as well

12. Ionization of Amino Acids
• Remember, amino acids without charged groups on side chain exist in neutral solution as zwitterions with no net charge

13. Titration of Amino Acids
• When an amino acid is titrated, the titration curve represents the reaction of each functional group with the hydroxide ion

14. Titration of histidine with NaOH

15. Ionization vs pH
Given the value of pKa of each functional group, we can calculate the ratio of each acid to its conjugate base as a function of pH
Consider the ionization of an -COOH
writing the acid ionization constant and rearranging terms gives (remember Ch. 2)

16. Ionization vs pH (cont’d)
substituting the value of Ka (1 x 10-2) for the hydrogen ion concentration at pH 7.0 (1.0 x 10-7) gives
at pH 7.0, the -carboxyl group is virtually 100% in the ionized or conjugate base form, and has a net charge of -1
we can repeat this calculation at any pH and determine the ratio of [-COO-] to [-COOH] and the net charge on the -carboxyl at that pH

17. Ionization vs pH (cont’d)
We can also calculate the ratio of acid to conjugate base for an -NH3+ group; for this calculation, assume a value 10.0 for pKa
writing the acid ionization constant and rearranging gives

18. Ionization vs pH
substituting values for Ka of an -NH3+ group and the hydrogen ion concentration at pH 7.0 gives
at pH 7.0, the ratio of -NH2 to -NH3 + is approximately 1 to 1000
at this pH, an -amino group is 99.9% in the acid or protonated form and has a charge of +1

19. Henderson-Hasselbalch Equation
We have calculated the ratio of acid to conjugate base for an -carboxyl group and an -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 (Ch. 2)

20. Isoelectric pH
Isoelectric pH, pI: the pH at which the majority of molecules of a compound in solution have no net charge
the pI for glycine, for example, falls midway between the pKa values for the carboxyl and amino groups
Isoelectric pH values for the 20 protein-derived amino acids are given in Table 3.2

21. Peptide Bonds
Individual amino acids can be linked by forming covalent bonds.
Peptide bond: the special name given to the amide bond between the -carboxyl group of one amino acid and the -amino group of another amino acid

22. Geometry of Peptide Bond
• the four atoms of a peptide bond and the two alpha carbons joined to it lie in a plane with bond angles of 120°about C and N
• to account for this geometry, a peptide bond is most accurately represented as a hybrid of two contributing structures (resonance structures)
• the hybrid has considerable C-N double bond character and rotation about the peptide bond is restricted

23. Resonance Structures of Peptide Bond

24. Peptides
• peptide: the name given to a short polymer of amino acids joined by peptide bonds; they are classified by the number of amino acids in the chain
• dipeptide: a molecule containing two amino acids joined by a peptide bond
• tripeptide: a molecule containing three amino acids joined by peptide bonds
• polypeptide: a macromolecule containing many amino acids joined by peptide bonds
• protein: a biological macromolecule of molecular weight 5000 g/mol or greater, consisting of one or more polypeptide chains

25. Problem set
Drawing 20 amino acids structure