peptide bond formation
Summary
Peptide bond formation joins the carboxyl group of one amino acid to the amino group of another, forming an amide bond and releasing H₂O (a condensation, or nucleophilic acyl substitution). Resonance gives the bond partial double-bond character, so it is planar with restricted rotation.
Detail
Meaning: Peptide bond formation links the carboxyl group of one amino acid to the amino group of another, making an amide bond and releasing water. It is a condensation (dehydration) reaction and a nucleophilic acyl substitution: the amine nitrogen attacks the carbonyl carbon and OH is lost. Resonance of the nitrogen lone pair with C=O gives the bond partial double-bond character, so it is planar with restricted rotation.
Equation: R–COOH + H₂N–R′ → R–CO–NH–R′ + H₂O, where R and R′ are the rest of each amino acid (no units). Uncoupled, the reaction is unfavorable (ΔG > 0); cells drive it with ATP-derived energy.
On the MCAT: Questions ask for the product of two amino acids, the water released (n residues in a linear chain form n − 1 bonds), and which end is the N-terminus or C-terminus. In synthesis passages a coupling reagent such as DCC activates the carboxyl group, and protecting groups prevent unwanted pairings.
Common confusion: Students treat the peptide bond as a freely rotating single bond or the amide nitrogen as basic. Resonance settles both: the C–N bond is partly double and the lone pair is delocalized, so rotation occurs about the N–Cα and Cα–C bonds.
Sources
- Organic Chemistry (Clayden, Greeves, Warren)
- Organic Chemistry (Wade)
- Lehninger Principles of Biochemistry
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.