A new tri-orthogonal strategy for peptide cyclization
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Updated: Sep 29, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Joseph T Lundquist1, Jeffrey C Pelletier
1Division of Discovery Chemistry, Wyeth Research, Collegeville, Pennsylvania 19426, USA. Lundquj@WAR.Wyeth.com
Abstract:
A solid phase tri-orthogonal protection/cleavage strategy that uses acidic, basic, and neutral conditions is described. Strategically protected alpha-azido-gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine (2) were incorporated into growing peptides on Wang resin using a novel azide protection strategy. These residues, separated by 1-3 monomers, were deprotected at the side chains and cyclized via lactam formation. The N-terminus was further functionalized to extend the chain. This method represents a straightforward protocol for peptide cyclization on solid support.
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