化学
二硫键
共价键
细胞内
组合化学
氨基酸
信使核糖核酸
立体化学
生物化学
有机化学
基因
作者
Steven W. Millward,Terry T. Takahashi,Richard W. Roberts
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.
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