Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling.

Details

Serval ID
serval:BIB_40146D7DD41B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling.
Journal
Molecular Immunology
Author(s)
Vyroubalova E.C., Hartley O., Mermod N., Fisch I.
ISSN
0161-5890 (Print)
ISSN-L
0161-5890
Publication state
Published
Issued date
04/2006
Volume
43
Number
10
Pages
1573-1578
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The determination of protein-protein interactions and their role in diverse pathophysiological processes is a promising approach to the identification of molecules of therapeutic potential. This paper describes the identification of peptidic CCR5 receptor ligands as potential drug leads against HIV-1 infection using in vitro evolution based on phage display. A phage-displayed peptide library was used to select for anti-CCR5 peptide. Further in vitro evolution of the peptide by exon shuffling was performed to identify peptides with optimized characteristics for CCR5 receptor. This peptide inhibited HIV coreceptor activity in a cell fusion assay with an IC50 of 5 microM. It did not exhibit either agonistic or antagonistic activity on CCR5 in the concentration range used. To our knowledge, this is a first report that describes the identification of peptide ligands specific to the CCR5 receptor from a phage-displayed library and the maturation of the selected peptide sequence by gene shuffling.
Keywords
Animals, Anti-HIV Agents/chemistry, Anti-HIV Agents/pharmacology, CHO Cells, Cells, Cultured, Cricetinae, Cricetulus, DNA Shuffling, Directed Molecular Evolution, Drug Design, Humans, Ligands, Membrane Fusion/drug effects, Peptide Library, Peptides/chemistry, Peptides/genetics, Receptors, CCR5/agonists, Receptors, CCR5/antagonists & inhibitors
Pubmed
Web of science
Create date
24/01/2008 11:41
Last modification date
20/08/2019 14:37
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