NOVEL INHIBITORS OF HIV RNA PROTEIN INTERACTIONS

HIV RNA 蛋白相互作用的新型抑制剂

• 批准号: 6213557
• 负责人: Maria L. Zapp
• 金额: $ 27.3万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6213557
• 关键词: Xenopus oocyte; antiAIDS agent; chemical structure function; circular dichroism; drug design /synthesis /production; drug interactions; human immunodeficiency virus 1; nuclear magnetic resonance spectroscopy; protein sequence; protein structure function; surface plasmon resonance; tissue /cell culture; virus RNA; virus protein; virus replication

DESCRIPTION (from applicant's abstract): The investigator proposes to continue analysis of the molecular basis of small molecules that selectively block the HIV-1 Rev-RRE interaction and Rev function. Attempts will be made to delineate the structure-function characteristics that govern RRE-aminoglycoside binding in vivo, to understand the effects of mutations in RRE that block aminoglycoside-binding on Rev function. These studies will then lead to the question of whether aminoglycoside-resistant RREs can emerge during viral replication and the fitness of such mutants. Furthermore, a newly identified diphenylfuran compound, as an inhibitor of Rev:RRE interacton will be further developed. First, the molecular basis of diphenylfuran:RRE interaction will be studied by a variety of spectroscopic methods, structure-activity relationship study will be performed to evolve compounds that are most effective in blocking viral replication. Finally, using small animal models, in vivo efficacy, pharmacokinetics and toxicity studies will be performed.

描述（来自申请人的摘要）：调查员建议继续 分析小分子的分子基础，这些分子有选择地阻止 HIV-1 Rev-RRE相互作用和Rev功能。将尝试划定 控制RRE-氨基糖苷结合的结构功能特征 在体内，了解RRE中突变的影响 Rev功能上的氨基糖苷结合。这些研究将导致 在病毒期间是否会出现抗氨基糖苷的RRE的问题 复制和这种突变体的适应性。此外，新近确定的 Diphenylfuran化合物，作为Rev：RRE Itsportiton的抑制剂，将进一步 发达。首先，二苯基富兰的分子基础：RRE相互作用将是 通过多种光谱方法研究，结构活性关系 将进行研究以发展最有效的化合物 病毒复制。最后，使用小动物模型，体内功效 将进行药代动力学和毒性研究。