Article thumbnail

Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor

By Jose ́ A. Esté, Cecilia Cabrera, Erik De Clercq, Sofie Struyf, Jo Van Damme, Gary Bridger, Renato T. Skerlj, Michael J. Abrams, Geoffrey Henson, Arantxa Gutierrez, Bonaventura Clotet and Dominique Schols

Abstract

Bicyclams represent a novel class of selective anti-HIV inhibi-tors with potent activity against T-cell tropic strains of HIV. The prototype compound, the bicyclam AMD3100, has an EC50 of 1 to 10 ng/ml against different strains of HIV-1, including clinical isolates. AMD3100 was shown to interact with the CXC-che-mokine receptor CXCR4, the main coreceptor used by T-cell tropic strains of HIV. Here we describe the interaction of differ-ent bicyclam derivatives with CXCR4. A close correlation (r2 5 0.7) was found between the anti-HIV potency of the bicyclams and their ability to inhibit the binding of an anti-CXCR4 mono-clonal antibody or the intracellular Ca11 signal induced by the stromal cell-derived factor-1a, the natural ligand of CXCR4. These results indicate that the mechanism of action of bicy-clams is primarily mediated by their interaction with CXCR4

Year: 1999
OAI identifier: oai:CiteSeerX.psu:10.1.1.932.7002
Provided by: CiteSeerX
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://molpharm.aspetjournals.... (external link)
  • http://molpharm.aspetjournals.... (external link)
  • http://citeseerx.ist.psu.edu/v... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.