Chemical synthesis of a cyclotide via intramolecular cyclization of peptide O-esters  

作　　者：ZHENG Ji-Shen CHANG Hao-Nan SHI Jing LIU Lei 

机构地区：[1]Department of Chemistry,University of Science and Technology of China,Hefei 230026,China Department of Chemistry,Tsinghua University,Beijing 100084,China [2]State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China

出　　处：《Science China Chemistry》2012年第1期64-69,共6页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(20932006,91013007);the National Basic Research Program of China(973 Program)(2011CB965300)

摘　　要：Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.

关 键 词：CYCLOTIDES chemical synthesis peptide O-ester native chemical ligation MACROLACTAMIZATION 

分 类 号：Q781[生物学—分子生物学] S565.101[农业科学—作物学]