A general route for post-translational cyclization of mRNA display libraries

被引:80
作者
Millward, SW [1 ]
Takahashi, TT [1 ]
Roberts, RW [1 ]
机构
[1] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
关键词
D O I
10.1021/ja054373h
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Cyclic peptides are attractive scaffolds for the design of conformationally constrained molecular therapeutics. Previously, biological display libraries could only be cyclized via disulfide bonds, which are labile and can be reduced in an intracellular environment. In this paper, we construct high diversity, covalently cyclized mRNA display libraries (> 1013 sequences) and analyze the cyclization reaction using MALDI-TOF MS and unnatural amino acid incorporation. Our route allows the extent of cyclization to be evaluated quantitatively and is broadly applicable to a variety of cyclization chemistries. Copyright © 2005 American Chemical Society.
引用
收藏
页码:14142 / 14143
页数:2
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