CATALYTIC RNA AND DNA AS ANTIHIV 1 THERAPEUTIC AGENTS

描述：(改编自申请者摘要)建议的研究目的 裂解DNA的RNA酶和裂解RNA的DNA酶在HIV-1中的应用 和FIV靶点，最终评估FIV的抗病毒效果 被感染的细胞。将开展药物生物化学项目， 解决复合效力、特异性、稳定性、传递和 配方。切割RNA的DNA酶将收到最大的 请注意。这些化合物只由30个脱氧核苷酸组成，但 其催化效率超过任何其他已知的核酸 酵素。DNA酶将被设计成切割FIV RNA中的靶点， 然后在感染了FIV的猫淋巴细胞中进行测试。 DNA酶也将被设计来裂解编码各种HIV-1的mRNAs 共同受体蛋白，这些分子将使艾滋病患者可用 研究社区，在研究中用作化学“击倒”试剂 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含有糖苷酶的DNA酶 活动。这种分子可能被用来裂解细胞表面的糖蛋白。 ，如HIV-1gp120囊膜糖蛋白。

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.