The amine capture strategy for peptide bond formation—an outline of progress

Abstract

AbstractA review is presented of the general features of amide bond formation by prior capture of the amine‐bearing peptide fragment. Capture by formation of a bond to the N‐terminal nitrogen is shown in eight model systems to result in slow intramolecular acyl transfer, accompanied by anomalously large Gly/Ala and Gly/Val rate ratios. Two examples are given of rapid intramolecular acyl transfer via rings of 9 and 12 members. The transfer efficiency as estimated by the effective molarity of reactive amine at the acyl carbon in the latter case is 18M. Capture at the thiol function of an N‐terminal cysteine residue is shown to be feasible in mercurithio and disulfide systems. In the latter case, effective concentrations of 3M and intramolecular transfer half‐times of 10 min are demonstrated.