Evaluation of "credit card" libraries for inhibition of HIV-1 gp41 fusogenic core formation
Evaluation of "credit card" libraries for inhibition of HIV-1 gp41 fusogenic core formation
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DOI：
10.1021/cc0600167
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发表时间：
2006-07-10
影响因子：
--
通讯作者：
Janda, Kim D.
中科院分区：
文献类型：
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作者：
Xu, Yang;Lu, Hong;Janda, Kim D.
蛋白质-蛋白质相互作用在生物系统中是至关重要的，并且这种蛋白质识别和干预过程的小分子调节剂是特别感兴趣的。为了研究这一领域的研究，我们合成了小分子文库，可以破坏许多生物相关的蛋白质-蛋白质相互作用。这些库成员被设计在平面基序上，附加有各种化学功能，我们称之为“信用卡”结构。从我们的两个“信用卡”库中，发现了一系列分子，它们在低微摩尔浓度下作为HIV-1 gp 41融合6-螺旋束核心形成、病毒抗原p24形成和细胞-细胞融合的抑制剂。从我们利用的高通量筛选测定中，发现化合物2261的选择性指数（SI）值为4.2，这预示着未来的结构活性研究和更有效的gp 41抑制剂的设计。
Protein-protein interactions are of critical importance in biological systems, and small molecule modulators of such protein recognition and intervention processes are of particular interest. To investigate this area of research, we have synthesized small-molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motif, appended with a variety of chemical functions, which we have termed "credit-card" structures. From two of our "credit-card" libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation, and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors.