Rider C C, Coombe D R, Harrop H A, Hounsell E F, Bauer C, Feeney J, Mulloy B, Mahmood N, Hay A, Parish C R
Department of Biochemistry, Royal Holloway and Bedford New College, Egham, Surrey, U.K.
Biochemistry. 1994 Jun 7;33(22):6974-80. doi: 10.1021/bi00188a029.
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.
（i）在体外抑制HIV-1复制，（ii）抑制针对V3环的单克隆抗体与重组HIV-1 gp120的结合。结果表明，N-去硫酸化会降低活性，不过在N-乙酰化后活性在很大程度上得以恢复。选择性O-去硫酸化也会显著降低活性，而羧基还原的影响较小。总体而言，这些结果表明肝素的抗HIV-1活性并非仅仅取决于负电荷密度，而是表明特定结构，尤其是O-硫酸盐，参与其中。我们的研究表明，对于化学修饰的肝素和肝素衍生片段，体外抗HIV-1活性与在固相ELISA中与gp120的V3环结合之间存在显著相关性。这有力地表明肝素通过与gp120的V3环结合发挥其抗HIV-1活性。
