In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation

doi:10.1007/s11427-007-0078-1

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	In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation
	Yan, Song ; Niu, RongLi ; Wang, Zheng ; Lin, XiuKun
	2007-10-01
发表期刊	SCIENCE IN CHINA SERIES C-LIFE SCIENCES
ISSN	1006-9305
卷号	50 期号:5 页码:630-636
文章类型	Article
摘要	Thymidylate synthase (TS), an essential enzyme for catalyzing the biosynthesis of thymidylate, is a critical therapeutic target in cancer therapy. Recent studies have shown that TS functions as an RNA-binding protein by interacting with two different sequences on its own mRNA, thus, repressing translational efficiency. In this study, peptides binding TS RNA with high affinity were isolated using mRNA display from a large peptide library (>10(13) different sequences). The randomized library was subjected up to twelve rounds of in vitro selection and amplification. Comparing the amino acid composition of the selected peptides (12th round, R12) with those from the initial random library (round zero, R0), the basic and aromatic residues in the selected peptides were enriched significantly, suggesting that these peptide regions might be important in the peptide-TS mRNA interaction. Categorizing the amino acids at each random position based on their physicochemical properties and comparing the distributions with those of the initial random pool, an obvious basic charge characteristic was found at positions 1, 12, 17 and 18, suggesting that basic side chains participate in RNA binding. Secondary structure prediction showed that the selected peptides of R12 pool represented a helical propensity compared with R0 pool, and the regions were rich in basic residues. The electrophoretic gel mobility shift and in vitro translation assays showed that the peptides selected using mRNA display could bind TS RNA specifically and inhibit the translation of TS mRNA. Our results suggested that the identified peptides could be used as new TS inhibitors and developed to a novel class of anticancer agents.; Thymidylate synthase (TS), an essential enzyme for catalyzing the biosynthesis of thymidylate, is a critical therapeutic target in cancer therapy. Recent studies have shown that TS functions as an RNA-binding protein by interacting with two different sequences on its own mRNA, thus, repressing translational efficiency. In this study, peptides binding TS RNA with high affinity were isolated using mRNA display from a large peptide library (>10(13) different sequences). The randomized library was subjected up to twelve rounds of in vitro selection and amplification. Comparing the amino acid composition of the selected peptides (12th round, R12) with those from the initial random library (round zero, R0), the basic and aromatic residues in the selected peptides were enriched significantly, suggesting that these peptide regions might be important in the peptide-TS mRNA interaction. Categorizing the amino acids at each random position based on their physicochemical properties and comparing the distributions with those of the initial random pool, an obvious basic charge characteristic was found at positions 1, 12, 17 and 18, suggesting that basic side chains participate in RNA binding. Secondary structure prediction showed that the selected peptides of R12 pool represented a helical propensity compared with R0 pool, and the regions were rich in basic residues. The electrophoretic gel mobility shift and in vitro translation assays showed that the peptides selected using mRNA display could bind TS RNA specifically and inhibit the translation of TS mRNA. Our results suggested that the identified peptides could be used as new TS inhibitors and developed to a novel class of anticancer agents.
关键词	Thymidylate Synthase Mrna Display Selection Affinity Peptides
学科领域	Biology
DOI	10.1007/s11427-007-0078-1
URL	查看原文
收录类别	SCI
语种	英语
WOS记录号	WOS:000250583300009
引用统计	被引频次：8[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/5704
专题	实验海洋生物学重点实验室
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Dalian Jiaotong Univ, Sch Environm Sci & Engn, Dalian 116028, Peoples R China
推荐引用方式 GB/T 7714	Yan, Song,Niu, RongLi,Wang, Zheng,et al. In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation[J]. SCIENCE IN CHINA SERIES C-LIFE SCIENCES,2007,50(5):630-636.
APA	Yan, Song,Niu, RongLi,Wang, Zheng,&Lin, XiuKun.(2007).In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation.SCIENCE IN CHINA SERIES C-LIFE SCIENCES,50(5),630-636.
MLA	Yan, Song,et al."In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation".SCIENCE IN CHINA SERIES C-LIFE SCIENCES 50.5(2007):630-636.

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