Synthesis of peptide macrocycles using unprotected amino aldehydes

被引:35
作者
Rotstein, Benjamin H. [1 ]
Rai, Vishal [1 ]
Hili, Ryan [1 ]
Yudin, Andrei K. [1 ]
机构
[1] Univ Toronto, Dept Chem, Davenport Res Labs, Toronto, ON M5S 1A1, Canada
关键词
CONFORMATIONAL-ANALYSIS; ISOCYANIDE SYNTHESIS; CYCLIC HEXAPEPTIDES; RACEMIZATION; TRIPEPTIDE; PHASE;
D O I
10.1038/nprot.2010.127
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
This protocol describes a method for synthesizing peptide macrocycles from linear peptide precursors, isocyanides and aziridine aldehydes. The effects of the reaction components on the efficiency of the process are discussed. Macrocyclization is exemplified by the preparation of a nine-membered ring peptide macrocycle. The product is further functionalized by nucleophilic opening of the aziridine ring with a fluorescent thiol. This transformation constitutes a useful late-stage functionalization of a macrocyclic peptide molecule. The experimental section describes the selection of the required starting materials, and the preparation of a representative aziridine-2-carboxaldehyde dimer. The synthesis and isolation of the peptide macrocycle can be accomplished in 6 h, and the ring-opening requires approximately 6-8 h. The aziridine-2-carboxaldehyde reagent is commercially available or can be synthesized from readily available starting materials in approximately 4 d. The strategy described is not limited to the specific peptide, isocyanide, aziridine aldehyde or nucleophile used in the representative synthesis.
引用
收藏
页码:1813 / 1822
页数:10
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