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Updated: May 24, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Postsynthetic modification of peptides via chemoselective N-alkylation of their side chains
Luca Monfregola1, Marilisa Leone, Enrica Calce
1Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
Abstract:
A chemoselective, mild, and versatile method for performing postsynthetic modifications of peptide sequences is described. It requires only activated molecular sieves in the presence of an alkyl halide in order to N-alkylate lysine side chains. This reaction is fully compatible with most of the peptide functionalities, discriminates the reactivity of differently protected lysines, and proceeds in good yield. The mild conditions employed were further proved by performing the N-alkylation of a peptide containing a disulfide bridge.
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