Chapter Three Amino Acids and Peptides

20 amino acids Titration of amino acids Peptide bond

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)

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.

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

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

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

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.

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

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

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

Titration of histidine with NaOH

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)

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

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

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

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)

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

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

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

Resonance Structures of Peptide Bond

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

Problem set Drawing 20 amino acids structure