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Updated: Jan 4, 2026

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
Published on: August 20, 2018
C-Terminal Modification of Fully Unprotected Peptide Hydrazides via in Situ Generation of Isocyanates
Alexander A Vinogradov1, Mark D Simon1, Bradley L Pentelute1
1Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Abstract:
A method for chemo- and regioselective conjugation of nucleophiles to fully unprotected peptides and proteins via in situ generation of C-terminal isocyanates is reported. Oxidation of C-terminal peptide hydrazides in aqueous media followed by Curtius rearrangement of acyl azides reliably generates isocyanates, which react with a variety of external nucleophiles, such as hydrazines, hydrazides, aromatic thiols, and hydroxylamines. Multiple peptides and a 53 kDa protein hydrazide were conjugated to different nucleophiles using this reaction.
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