Anti-HIV-1 Activity of Chemically Modified Heparins: Correlation between Binding to the V3 Loop of gp120 and Inhibition of Cellular HIV-1 Infection in vitro

作者：Christopher C. Rider, Deirdre R. Coombe, Hilary A. Harrop, Elizabeth F. Hounsell, Christopher J. Bauer, James Feeney, Barbara Mulloy, Naheed Mahmood, Alan J Hay, Christopher R. Parish · 发表于：Biochemistry · 年份：1994 · DOI：10.1021/bi00188a029 · 被引用次数：73 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Carbohydrate Chemistry and Synthesis

Chemically modified heparins were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting the binding to recombinant HIV-1 gp120 of monoclonal antibodies specific for the V3 loop. The results reveal that N-desulfation reduces activity, although this is largely restored on N-acetylation. Selective O-desulfation also markedly reduces activity, whereas carboxyl reduction has little effect. Overall these results show that the anti-HIV-1 activity of heparin does not depend simply on negative density, and indicate instead that particular structures, notably O-sulfates, are involved. Our studies reveal that for chemically modified heparins and heparin-derived fragments there is a striking correlation between anti-HIV-1 activity in vitro and binding to the V3 loop of gp120 in solid phase ELISA. This strongly suggests that the heparin exerts its anti-HIV-1 activity by binding to the V3 loop of gp120.