A new strategy for synthesis of branched cyclic peptide by Asn side-chain hydrazide ligation

Here, we report a new strategy for rapid synthesis of branched peptide by side-chain hydrazide ligation at Asn. The hydrazide was converted to thioester at Asn side chain by NaNO2 and thiol reagent, and sequential ligation with an N-terminus Cys-peptide efficiently afforded the branched peptide. A branched cyclic peptide was successfully synthesized by side-chain ligation with a two-Cys-peptide and formation of a disulfide bond. This approach provides a new way for expeditious synthesis of branched peptides and facilitates the design of neopeptides as functional bio-mimics.

Graphical abstractWe report here a new synthetic method of branched peptide by ligation of Asn side-chain hydrazide with an N-terminus Cys peptide. The peptide branch containing a disulfide bond displays a cyclic loop for special neopeptide design.Figure optionsDownload full-size imageDownload as PowerPoint slide