Efficient enzyme-catalyzed synthesis of peptide secondary amides for use as serine proteinase inhibitors

An efficient and straightforward approach toward enzymatic synthesis of secondary amides of peptides was developed. A number of peptide derivatives containing amide moiety at C-terminus was obtained via subtilisin catalysis in good yields under mild conditions. Biological activity of some peptamides is evaluated.

General reaction scheme for the synthesis of peptide secondary amide derivatives (PG: protecting group; Xaa, Xbb and Xcc: amino acid residues in l-configuration; R1 and R2 are hydrocarbon radicals which can be substituted or taken together with the nitrogen atom form optionally substituted heterocycle).Figure optionsDownload as PowerPoint slideHighlights
► We developed new enzyme-catalyzed route to synthesis of peptamides.
► A number of peptamides with various amino-acid sequence is synthesized.
► Biological activity of some peptamides is evaluated.