peptide chemistry

Meaning: Peptide chemistry is the chemistry of amino acids joined by amide bonds. The α-amine of one amino acid acts as a nucleophile and attacks the carbonyl carbon of another's carboxyl group (nucleophilic acyl substitution), and water is lost in this condensation. In the lab, a coupling reagent such as DCC activates the carboxyl group, and protecting groups such as Boc or Fmoc block groups that should not react. Resonance delocalizes the nitrogen lone pair into the C=O, giving the C–N bond partial double-bond character. The bond is therefore planar and its rotation is restricted.

Equation: R–COOH + H₂N–R′ → R–CO–NH–R′ + H₂O, where R and R′ are the remaining parts of the two molecules. A linear chain of n residues has n − 1 peptide bonds (n is a unitless count).

On the MCAT: Expect questions on which atom is the nucleophile, why protecting groups are needed, the products of acid hydrolysis, and N-terminus to C-terminus order.

Common confusion: The amide nitrogen is not basic like an amine, because its lone pair is delocalized by resonance, so it is not protonated near physiological pH. Only the free N-terminal amine and C-terminal carboxyl group ionize in the backbone.