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Updated: Jun 2, 2026
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
On resin side-chain cyclization of complex peptides using CuAAC
Sampat Ingale1, Philip E Dawson
1Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Organic Letters
|May 11, 2011
Summary
This study introduces a new on-resin method for efficiently stabilizing peptide structures using triazole tethers. The protocol enhances cyclization for complex peptides, including those targeting HIV-1 gp41.
Area of Science:
- Medicinal Chemistry
- Organic Chemistry
- Biochemistry
Background:
- Triazole tethers are used to stabilize peptide secondary structures.
- Efficient cyclization of complex peptides remains a challenge.
Purpose of the Study:
- To develop a robust on-resin protocol for side chain to side chain macrocyclization using copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC).
- To synthesize and stabilize helical peptides from the HIV-1 gp41 membrane proximal external region (MPER).
Main Methods:
- Development of an on-resin macrocyclization protocol.
- Application of the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction.
- Synthesis of 21-amino acid helical peptides.
Main Results:
- A robust on-resin protocol for macrocyclization was established.
- The protocol demonstrated high efficiency in synthesizing complex helical peptides.
- The synthesized peptides feature a binding motif from HIV-1 gp41 MPER.
Conclusions:
- The described on-resin CuAAC protocol is effective for stabilizing complex peptide secondary structures.
- This method facilitates the synthesis of peptides with potential therapeutic applications, such as those targeting HIV-1.
- The approach offers a significant advancement in peptide cyclization efficiency.
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