HIV-1 PG120 V3 LOOP TARGETING--NOVEL POTENTIAL INHIBITOR

描述：母基金（CA43315-09）涉及合成 针对V3环的抗病毒化合物，其定义 结构-功能关系，评估其抗病毒活性 针对主要 HIV-1 分离株，以及具有活性的化合物的设计 导致与 gp120/41 不可逆结合的基团。拟议的 FIRCA 目标是合成（a）新的卟啉衍生物，（b） 具有各种呋喃戊糖基的硫代磷酸胞嘧啶寡核苷酸 构型和磷酸胞嘧啶寡核苷酸 疏水性官能团插入到附近 膦酸酯部分，和（c）卟啉衍生物的缀合物和 寡核苷酸。合成分子的体外测试 抗HIV作用及其与gp120和V3环的结合将完成 作为家长补助金的一部分。国外合作者（主要 研究员）是有机研究所的 Ivan Rosenberg 博士 布拉格的化学和生物化学，由博士协助。托西克、利博斯卡和 恩多瓦。

DESCRIPTION: The parent grant (CA43315-09) deals with the synthesis of antiviral compounds targeted to the V3 loop, the definition of their structure-function relationships, assessment of their antiviral activity against primary HIV-1 isolates, and the design of compounds with reactive groups leading to irreversible binding to gp120/41. The proposed FIRCA aims are the synthesis of (a) new porphyrin derivatives, (b) phosphorothioate cytosine oligonucleotides with various pentofuranosyl configurations and phosphonate cytosine oligonucleotides with hydrophobic functional groups inserted in the vicinity of the phosphonate moieties, and (c) conjugates of the porphyrin derivatives and oligonucleotides. The in vitro testing of the synthesized molecules for anti-HIV effect and their binding to gp120 and the V3 loop will be done as part of the parent grant. The foreign collaborator (principal investigator) is Dr. Ivan Rosenberg of the Institute of Organic Chemistry and Biochemistry in Prague, assisted by Drs. Tocik, Liboska and Endova.