Novel targets for HIV-1: Tat-TAR interactions

描述（申请人提供）：人类免疫缺陷病毒 I型（HIV-1）是编码六种调节蛋白的复杂逆转录病毒， 包括达特。达特蛋白是一种有效的转录激活因子， HIV-1长末端重复启动子元件。+1之间的调节元件 和+60在HIV-1`长末端重复，能够形成稳定的 命名为TAR的茎环结构对于达特功能至关重要。在 达特缺失时，RNA聚合酶II（pol II）终止转录 过早地。Tat-TAR相互作用有助于转化pol II与RNA的相互作用 模板转化为有效产生的全长病毒转录物。我们有 最近证明，由三肽组成的组合文库 含有不仅与TAR结合而且抑制达特的分子 与焦油的相互作用和随后的LTR指导的转录减少， 细胞培养这项研究的目标是发现低 通过结合抑制HIV复制的分子量非肽化合物 TAR RNA元件。这项研究的成功将为新的 发现与离散RNA结构结合的药物的机会 可能应用于诸如癌症和艾滋病的疾病。 拟议商业应用：不可用

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