DESIGN OF UMAN PAPILLOMAVIRUS INHIBITORS

乌曼乳头状病毒抑制剂的设计

• 批准号: 6373476
• 负责人: JAMES D BALEJA
• 金额: $ 35.96万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373476
• 关键词: antiviral agents; drug discovery /isolation; human papillomavirus; nuclear magnetic resonance spectroscopy; protein structure; structural biology; virus protein

In this revised competitive grant application Dr. Baleja describes studies designed to identify small molecule inhibitors of the E6 oncoprotein of human papillomaviruses associated with cervical cancer. The identification of these inhibitors shall be based upon structural information obtained for small peptides from E6AP and E6BP that mediate the binding of these cellular factors to E6. Proof of principle studies are now provided in the revised grant application as is additional NMR based structural information regarding the E6AP and E6BP peptides. Small molecules will be characterized for their capacity to interfere with E6 function in vitro, in tissue culture, and ultimately in animal models. A second aim is refocused on trying to modify tatE2 fusion peptides that have proven of moderate value in inhibiting the function of the E2 transcriptional transactivator. These modifications are designed to improve DNA binding activity and alter dimerization properties so as to increase the effectiveness of the fusion protein in inhibiting E2TA function and in repressing transcription of the E6 and E7 genes.

在此修订的竞争赠款申请中，Baleja博士描述了 旨在鉴定E6癌蛋白的小分子抑制剂的研究 与宫颈癌相关的人乳头瘤病毒。识别 这些抑制剂应基于对小的结构信息 来自E6AP和E6BP的肽介导这些细胞因子的结合 到E6。现在在修订的赠款中提供了原则研究证明 与其他基于NMR的结构信息有关 E6AP和E6BP肽。小分子将以它们的特征 在体外，组织培养和 最终在动物模型中。第二个目标是重新集中于尝试修改 Tate2融合肽在抑制中具有适中价值的肽 E2转录反式激活器的功能。这些修改是 旨在改善DNA结合活性并改变二聚化特性 为了提高融合蛋白抑制E2TA的有效性 功能和抑制E6和E7基因的转录。