A General Route for Post-Translational Cyclization of mRNA Display Libraries

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• 作者：Steven W. Millward ; Terry T. Takahashi ; and Richard W. Roberts
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：October 19, 2005
• 年：2005
• 卷：127
• 期：41
• 页码：14142 - 14143
• 全文大小：81K
• 年卷期：v.127,no.41(October 19, 2005)
• ISSN：1520-5126

文摘

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.