Chemoenzymatic Posttranslational Modification Reactions for the Synthesis of Ψ[CH2 NH]-Containing Peptides.

The Ψ[CH2 NH] reduced amide bond is a peptide isostere widely used in the development of bioactive pseudopeptides. Reported here is a method of chemoenzymatic posttranslational modification for the synthesis of Ψ[CH2 NH]-containing peptides converted from ribosomally expressed peptides. The posttranslational conversion composed of an enzymatic cyclodehydration and facile two-step chemical reduction achieves deoxygenation of a specific amide bond present in a nonprotected peptide in water. This method generates the Ψ[CH2 NH] bond in peptides and is applicable to various peptide sequences, potentially enabling the preparation of a library of Ψ[CH2 NH]-containing peptides.