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Chem Biol Drug Des. 2008 Aug;72(2):97-110. doi: 10.1111/j.1747-0285.2008.00681.x. Epub 2008 Jul 9.

CXCR4, inhibitors and mechanisms of action.

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1
Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, MO 65211, USA. liangxi@missouri.edu

Abstract

In this review, the author discusses recent advances in anti-HIV inhibitors, targeting CXCR4, including natural and modified chemokines, peptides and organic compounds, their mechanisms of action, and the molecular process of virus invasion of immune cells. Peptides with strong anti-HIV activity exhibit several common features, such as electrostatic charges, cyclization, beta-turns and dimerization induced by a sulphide bond. Organic compounds, such as cyclams, display a unique metal-mediated mechanism in the binding process to its target CXCR4. Understanding of their mechanisms of action may be useful for the design of more effective drugs. Consecutive interactions of viral glycoprotein gp120 with CD4 and the co-receptor, CXCR4 or another co-receptor CCR5 on the cell surface leads to virus invasion into host cells. The molecular details of the binding between HIV glycoproteins and the co-receptors also provide a basis for anti-HIV therapy.

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