A peptide bond is the amide linkage formed when the carboxyl group of one amino acid condenses with the amino group of the next, releasing a molecule of water. It is the covalent backbone of every peptide, and its physical properties explain much of what peptide chemists design around.
Structure and consequences
Resonance gives the C–N bond partial double-bond character, so the amide unit is planar and rotation about it is restricted; conformational freedom lives in the flanking phi and psi angles instead. That planarity is why backbones fold into predictable helices and turns. The bond is thermodynamically unstable to hydrolysis but kinetically very slow — uncatalysed half-lives at neutral pH are measured in centuries — so in biological media proteases, not water, are the practical route of breakdown.
Why it matters
Every strategy for extending peptide half-life targets this backbone or its neighbours: D-amino acid substitution, Aib insertion, N-terminal acetylation, C-terminal amidation, or fatty-acid acylation that promotes albumin binding. In manufacture, forming one bond is the repeated step of solid-phase peptide synthesis; incomplete coupling at any position leaves deletion sequences that appear as shoulder peaks on HPLC and as mass gaps on MS.
Related terms
amino acid · degradation · disulfide bridge. Further reading: peptide stability and half-life.