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A synthetic CD4-heparan sulfate glycoconjugate inhibits CCR5 and CXCR4 HIV-1 attachment and entry.

Abstract : The HIV-1 envelope, gp120, which features the binding determinants for both CD4 and coreceptor recognition, is key for virus entry and represents an attractive pharmacological target. However, critical domains for entry (coreceptor and CD4 binding sites) are either cryptic or located in partially occluded cavities. Here we developed a chemical approach to synthesize a CD4-mimetic peptide linked to a heparan sulfate dodecasaccharide. This molecule binds to gp120, induces the exposure of the coreceptor binding domain and renders it available for interaction with the oligosaccharide. The linkage between the CD4 mimetic and the heparan sulfate derivative provides strong cooperative effects, resulting in low-nanomolar antiviral activity toward both CCR5- and CXCR4-tropic HIV-1 strains. This compound, which has the unique ability to simultaneously target two critical and highly conserved regions of gp120, establishes a new type of inhibitor and suggests a general concept for the inhibition of numerous other biological systems.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00415325
Contributor : Françoise Baleux <>
Submitted on : Thursday, September 10, 2009 - 2:58:19 PM
Last modification on : Wednesday, October 14, 2020 - 4:17:39 AM

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Françoise Baleux, Latino Loureiro-Morais, Yael Hersant, Pascal Clayette, Fernando Arenzana-Seisdedos, et al.. A synthetic CD4-heparan sulfate glycoconjugate inhibits CCR5 and CXCR4 HIV-1 attachment and entry.. Nature Chemical Biology, Nature Publishing Group, 2009, epub ahead of print. ⟨10.1038/nchembio.207⟩. ⟨pasteur-00415325⟩

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