Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120.
Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120.
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硫代磷酸酯寡脱氧核苷酸与人类免疫缺陷病毒 1 型 gp120 的第三可变环结构域 (v3) 结合。
DOI：
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Seth Lederman
中科院分区：
文献类型：
--
作者：
Cy A. Stein;A. Cleary;Leonid Yakubov;Seth Lederman
尽管在一级序列中具有可变性，但在人类免疫缺陷病毒1型（HIV-1）的致病株中gp 120的v3环带正电荷，并且已知与硫酸化多糖相互作用。由于硫酸多糖与v3环的相互作用在体外抑制HIV感染，我们研究了v3环与磷酸二酯（PO）和硫代磷酸（PS）寡脱氧核苷酸（oligos）的相互作用。在固相ELISA测定中，PS 28聚体的胞苷，SdC 28的均聚物，阻断的v3环特异性单克隆抗体（mAb）9284的结合，以rgp 120更有力地比葡聚糖硫酸。此外，与硫酸葡聚糖一样，SdC 28似乎特异性结合v3环，因为这两种化合物都不抑制其他抗gp 120 mAb的结合。与PS寡核苷酸相反，PO寡核苷酸不抑制mAb 9284结合。利用一系列PS寡核苷酸研究了PS寡核苷酸与v3环相互作用的长度依赖性。抑制活性的离散损失发生作为减少PS寡核苷酸长度的函数，这是最显着的PS寡核苷酸的18聚体和12聚体的长度之间。我们通过测量不同长度的PS和PO寡核苷酸的gp 120结合亲和力，进一步探讨了寡核苷酸与gp 120相互作用的化学性质。我们采用了5 ′-32 P标记的烷基化寡核苷酸ClRNH 32 P-OdT 15，并确定gp 120结合的Km为4 μ M。我们还测定了ClRNH 32 P-OdT 15结合的PS竞争者的竞争常数（Kc）值。PS寡核苷酸的结合常数（= 1/Kc）显示，对于长度> 12- 18-mer的PS寡核苷酸，gp 120结合的离散增加，超过18-mer没有进一步的增加。鉴于v3环在HIV-1致病性中的重要作用，这些数据表明应考虑PS寡核苷酸的治疗试验。
Although having variability in primary sequence, the v3 loop of gp120 in pathogenic strains of human immunodeficiency virus type-1 (HIV-1) is positively charged and known to interact with sulfated polysaccharides. Because the interaction of sulfated polysaccharides with the v3 loop inhibits HIV infection in vitro, we investigated the interaction of the v3 loop with phosphodiester (PO) and phosphorothioate (PS) oligodeoxynucleotides (oligos). In a solid-phase ELISA assay, a PS 28-mer homopolymer of cytidine, SdC28, blocked the binding of the v3 loop-specific monoclonal antibody (mAb) 9284 to rgp120 more potently than did dextran sulfate. In addition, like dextran sulfate, SdC28 appeared to bind specifically to the v3 loop, because neither compound inhibited the binding of other anti-gp120 mAbs. In contrast to PS oligos, PO oligos did not inhibit mAb 9284 binding. The length dependence of the interaction of PS oligos with the v3 loop was studied by using a series of PS oligos. A discrete loss of inhibiting activity occurred as a function of decreasing PS oligo length, which was most marked between PS oligos of 18-mer and 12-mer in length. We further probed the chemical nature of the interaction of oligos with gp120 by measuring the gp120 binding affinities of PS and PO oligos of various lengths. We employed a 5'-32P-labeled alkylating oligo, ClRNH32P-OdT15, and determined that the Km of gp120 binding is 4 microM. We also determined values of competition constant (Kc) for PS competitors of ClRNH32P-OdT15 binding. The binding constant (= 1/Kc) for PS oligos showed a discrete increase in gp120 binding for PS oligos > 12- to 18-mer in length, with no further increment beyond an 18-mer. Given the important role of the v3 loop in HIV-1 pathogenicity, these data suggest that therapeutic trials of PS oligos should be considered.
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影响因子：
4.4
作者：
Seth Lederman;Roy M. Gulick;Leonard Chess
通讯作者：
Seth Lederman;Roy M. Gulick;Leonard Chess
影响因子：
56.9
作者：
KOWALSKI, M;POTZ, J;SODROSKI, J
通讯作者：
SODROSKI, J
人单克隆抗体，可识别人类免疫缺陷病毒 gp120 的 V3 区并中和人类嗜 T 淋巴细胞病毒 IIIMN 型毒株。
DOI：
10.1073/pnas.87.21.8597
发表时间：
1990
影响因子：
11.1
作者：
ScottJr,CF;Silver,S;Profy,AT;Putney,SD;Langlois,A;Weinhold,K;Robinson,JE
通讯作者：
Robinson,JE
硫酸化聚酯与 CD4 分子和 gp120 第三可变环结构域 (v3) 的相互作用在化学上是不同的。
影响因子：
1.5
作者：
Lederman,S;Bergmann,JE;Cleary,AM;Yellin,MJ;Fusco,PJ;Chess,L
通讯作者：
Chess,L