STRUCTURAL STUDIES OF CD4 COMPLEXES

CD4 复合物的结构研究

• 批准号: 6099272
• 负责人: STEPHEN COPLAN HARRISON
• 金额: --
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1998-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099272
• 关键词: CD4 molecule; HIV envelope protein gp120; X ray crystallography; antiAIDS agent; antiviral agents; computer program /software; conformation; cooperative study; crystallization; human immunodeficiency virus 1; monoclonal antibody; protein structure; structural biology

The approaches outlined in Part I suggest new routes to obtaining homogeneous complexes of CD4 and HIV gp120. Crystallization of these complexes, which involve the two-domain fragment CD4 (1-183) and various deglycosylate and truncated derivatives of gp120, will be attempted. The goal is determination of a three-dimensional structure of the CD4/gp120 complex by X-ray diffraction to whatever resolution the crystals will afford. Further knowledge of the structure of this complex will be important for design of compounds that block viral attachment or that inactivate HIV by mimicking CD4. In addition, efforts will be made to determine the structure of complexes of CD4 (1-183) with compounds already available that interfere with the CD4/gp120 interaction. Two strategies will be attempted: co-crystallization of the compounds with CD4(1-183), and diffusion of the compounds into CD4(1-183)/Fab co- crystals. The determination of one or more such structures will permit more rational design of actual drug candidates.

第一部分中概述的方法建议获得新的途径 CD4和HIV GP120的均匀复合物。 这些的结晶 复合物，涉及两域片段CD4（1-183）和各种 将尝试脱糖基酯和截短的GP120衍生物。 这 目标是确定CD4/GP120的三维结构 复合X射线衍射到晶体所需的任何分辨率 买得起。 进一步了解该建筑群的结构将是 对于阻断病毒附着的化合物的设计很重要或 通过模仿CD4灭活HIV。 此外，将努力 确定具有化合物CD4（1-183）的复合物的结构 已经干扰CD4/GP120相互作用了。 二 将尝试策略：与化合物的共结晶与 CD4（1-183），并将化合物扩散到CD4（1-183）/Fab Co- 晶体。 确定一个或多个这样的结构将允许 实际候选毒品的更合理设计。