peptide phage display as a tool for drug discovery targeting membrane receptors噬菌体展示肽作为药物发现工具针对膜受体.pdfVIP

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peptide phage display as a tool for drug discovery targeting membrane receptors噬菌体展示肽作为药物发现工具针对膜受体.pdf

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peptide phage display as a tool for drug discovery targeting membrane receptors噬菌体展示肽作为药物发现工具针对膜受体

Molecules 2011, 16, 857-887; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Peptide Phage Display as a Tool for Drug Discovery: Targeting Membrane Receptors Peter Molek 1, Borut Strukelj 1,2 and Tomaz Bratkovic 1,* 1 Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia 2 Department of Biotechnology, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia * Author to whom correspondence should be addressed; E-Mail: tomaz.bratkovic@ffa.uni-lj.si; Tel.: +386-1-47-69-500; Fax: +386-1-42-58-031. Received: 7 December 2010; in revised form: 14 January 2011 / Accepted: 19 January 2011 / Published: 21 January 2011 Abstract: Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Consequently, peptides derived from library screenings often modulate the target protein’s activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. This review discusses the use of phage display to identify membrane receptor modulators with agonistic or antagonistic activities. Because isolating or producing recombinant membrane proteins for use as target molecules in library screening is often impossible, innovative selection