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

被引：5

作者：

Fan, Lijun ^{[1
]}

Yu, Yang ^{[1
]}

Jayne, Charles ^{[1
]}

Frost, John R. ^{[1
]}

Scott, Jack D. ^{[1
]}

机构：

[1] Merck & Co Inc, Rahway, NJ 07065 USA

来源：

ORGANIC LETTERS | 2023年 / 25卷 / 44期

关键词：

D O I：

10.1021/acs.orglett.3c03284

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：8038 / 8042

页数：5

共 25 条

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