Novel targets for HIV-1: Tat-TAR interactions

HIV-1 的新靶标：Tat-TAR 相互作用

• 批准号: 6405888
• 负责人: Robert Rando
• 金额: $ 14万
• 依托单位: PTC THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6405888
• 关键词: DNA directed RNA polymerase; antiAIDS agent; antiviral agents; combinatorial chemistry; drug design /synthesis /production; human immunodeficiency virus 1; nucleic acid repetitive sequence; peptide library; protein protein interaction; virus protein; virus replication

DESCRIPTION (Provided by the applicant): The human immunodeficiency virus type-i (HIV-i) is a complex retrovirus that encodes six regulatory proteins, including Tat. The Tat protein is a potent transcriptional activator of the HIV-1 long terminal repeat promoter element. A regulatory element between +1 and +60 in the HIV-1`long terminal repeat which is capable of forming a stable stem-loop structure, designated TAR, is critical for Tat function. In the absence of Tat, RNA polymerase II (pol II) terminates transcription prematurely. Tat-TAR interactions help convert pol II interactions with the RNA template into efficiently produced full-length viral transcripts. We have recently demonstrated that combinatorial libraries composed of tripeptides contained molecules that not only bound to TAR but also inhibited Tat interaction with Tar and subsequent LTR directed transcription was reduced in cell culture. The goal of the proposed research is the discovery of low molecular weight non-peptide compounds that inhibit HIV replication by binding to the TAR RNA element. The success of this research would open the door to new opportunities in the discovery of drugs which bind to discrete RNA structures with possible applications for diseases such as cancer and aids. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请人提供）：人类免疫缺陷病毒