Synthesis of DNA-Encoded Macrocyclic Peptides via Nitrile-Aminothiol Click Reaction

DNA-encoded library (DEL) technology holds exciting potential for discovering novel therapeutic macrocyclic peptides (MPs). Herein, we describe the development of a DEL-compatible peptide macrocyclization method that proceeds via intramolecular click-condensation between 3-(2-cyano-4-pyridyl)-l-alan...

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Published in:Organic letters 2023-11, Vol.25 (44), p.8038-8042
Main Authors: Fan, Lijun, Yu, Yang, Jayne, Charles, Frost, John R., Scott, Jack D.
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Language:English
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container_end_page 8042
container_issue 44
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container_title Organic letters
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creator Fan, Lijun
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description DNA-encoded library (DEL) technology holds exciting potential for discovering novel therapeutic macrocyclic peptides (MPs). Herein, we describe the development of a DEL-compatible peptide macrocyclization method that proceeds via intramolecular click-condensation between 3-(2-cyano-4-pyridyl)-l-alanine (Cpa) and an N-terminal cysteine. Cyclization takes place spontaneously in a buffered aqueous solution and affords the cyclized products in excellent yields. The reaction exhibits a broad substrate scope and can be employed to generate MPs of variable ring size and amino acid composition.
doi_str_mv 10.1021/acs.orglett.3c03284
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title Synthesis of DNA-Encoded Macrocyclic Peptides via Nitrile-Aminothiol Click Reaction
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