Synthesis and Anti-HIV Activity of a Series of 6-Modified 2＇,3＇-Dideoxyguanosine and 2＇,3＇-Didehydro-2＇,3＇- dideoxyguanosine Analogs  

作　　者：Lujia Xie Xiantao Yang Delin Pan Yingli Cao Mou Cao Guichun Lin Zhu Guan Ying Guo Lihe Zhang Zhenjun Yang 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China [2]Institute ofMateria Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出　　处：《Chinese Journal of Chemistry》2013年第9期1207-1218,共12页中国化学（英文版）

基　　金：The research was supported by the fund of the National Natural Science Foundation of China，the Ministry of Science and Technology of China (No.2008ZX10303).Anti-HIV activity evaluation in pseudotyped HIV system was performed by Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College.Anti-HIV activity evaluation in HIV-1/MT2 cells was performed by HD

摘　　要：In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.

关 键 词：2＇ 3＇-dideoxyguanosine （ddG） 2＇ 3＇-didehydro-2＇ 3＇-dideoxyguanosine （D4G） PRODRUG anti-HIV activity 

分 类 号：Q78[生物学—分子生物学] TQ463.24[化学工程—制药化工]