CATALYTIC RNA AND DNA AS ANTIHIV 1 THERAPEUTIC AGENTS

描述：（改编自申请人摘要）拟定的研究目的 将DNA切割RNA酶和RNA切割DNA酶应用于HIV-1 和FIV靶点，最终评估FIV中的抗病毒疗效 被感染的细胞 将开展药物生物化学项目， 解决了化合物效力、特异性、稳定性、递送和 公式化。 切割RNA的DNA酶将获得最大的 关注 这些化合物仅由30个脱氧核苷酸组成， 具有超过任何其它已知核酸的催化效率 酵素 DNA酶将被设计成切割FIV RNA内的靶位点， 然后在已感染FIV的猫淋巴细胞中进行测试。 DNA酶也将被设计成切割编码各种HIV-1的mRNA。 辅助受体蛋白质，这些分子将提供给艾滋病 研究界作为一种化学“淘汰”剂，在研究 β趋化因子受体在HIV-1发病机制中的作用。 最后在 体外进化方法将用于开发具有糖苷酶的DNA酶 活动 这些分子可能被用来切割细胞表面的糖蛋白 ，例如HIV-1 gp 120包膜糖蛋白。

DESCRIPTION: (Adapted from Applicant's Abstract) The proposed research aims to apply the DNA cleaving RNA enzymes and RNA cleaving DNA enzymes to HIV-1 and FIV targets, culminating in an assessment of antiviral efficacy in FIV infected cells. A program of medicinal biochemistry will be carried out, addressing issues of compound potency, specificity, stability, delivery, and formulation. The RNA cleaving DNA enzymes will receive the greatest attention. These compounds are comprised of only 30 deoxynucleotides, yet have a catalytic efficiency exceeding that of any other known nucleic acid enzyme. DNA enzymes will be designed to cleave target sites within FIV RNA, then tested in feline lymphocytic cells that have been infected with FIV. DNA enzymes also will be designed to cleave mRNAs encoding various HIV-1 co-receptor proteins, These molecule will be made available to the AIDS research community for use as a chemical "knock out" agents in studying the role that beta chemokine receptors play in HIV-1 pathogenesis. Finally, in vitro evolution methods will be used to develop DNA enzymes with glycosidase activity. Such molecules might be used to cleave cell-surface glycoproteins , such as the HIV-1 gp 120 envelope glycoproteins.