期刊
JOURNAL OF PEPTIDE SCIENCE
卷 14, 期 8, 页码 924-935出版社
WILEY
DOI: 10.1002/psc.1027
关键词
HIV RRE RNA; arginine-rich peptide; combinatorial analysis; antitermination system; anti-HIV drugs
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
The arginine-rich motif is a class of short arginine-rich peptides that bind to specific RNA structures that has been found to be a versatile framework for the design and selection of RNA-binding peptides. We previously identified novel peptides that bind to the Rev-response element (RRE) RNA of the HIV from an arginine-rich polypeptide library (ARPL) consisting of a polyarginine (15 mer) randomized at the N-terminal 10 positions. The selected peptides bound more strongly to the RRE than the natural binding partner. Rev. and contained glutamine residues that: were assumed to be important for recognition of the G-A base pair. In addition, the peptides were predicted to bind to the RRE in an a-helical conformation. In this study. in order to understand the mechanism of the interaction between the RRE and the putative a-helical glutamine-containing peptides. the amino acid requirements for high affinity binding were analyzed by a combinatorial approach using a bacterial system for detecting RNA-peptide interactions. A consensus peptide. the DLA peptide, was elucidated, which consists of a single glulamine residue within a polyarginine context. with the glulamine residue flanked at specific positions by three nonarginine residues. two of which appear to be important for a-helix stabilization. In addition. the DLA peptide was found to bind extremely tightly to the RRE with an affinity 50-fold higher than that of the Rev peptide as determined by a gel shift assay. A working model for the interaction of the DLA peptide to the RRE is proposed. which should aid in the development of peptide-based drugs that inhibit HIV replication, as well as in our understanding of polypeptide-RNA interactions. Copyright (C) 2008 European Peptide Society and John Wiley & Sons. Ltd.
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