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Title

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

Authors
Vyroubalova, Eva Cachin
Mermod, Nicolas
Fisch, Igor
Published in Molecular Immunology. 2006, vol. 43, no. 10, p. 1573-8
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 AnimalsAnti-HIV Agents/chemistry/pharmacologyCHO CellsCellsCulturedCricetinaeCricetulusDNA ShufflingDirected Molecular EvolutionDrug DesignHumansLigandsMembrane Fusion/drug effectsPeptide LibraryPeptides/chemistry/genetics/pharmacologyReceptorsCCR5/agonists/antagonists & inhibitors/drug effects
Identifiers
PMID: 16280164
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Research group HIV (835)
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VYROUBALOVA, Eva Cachin et al. Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling. In: Molecular Immunology, 2006, vol. 43, n° 10, p. 1573-8. https://archive-ouverte.unige.ch/unige:26026

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Deposited on : 2013-01-30

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