文献类型：期刊文献

中文题名：化学酶法合成抗病毒药物2’,3’-双脱氧腺苷

英文题名：Chemo-Enzymatic Synthesis of Antivirus Agent Deoxyadenosine

作者：辛自豪[1];丁庆豹[1];欧伶[1];邱蔚然[2]

机构：[1]华东理工大学生物反应器工程国家重点实验室,上海200237;[2]南通秋之友生物科技有限公司,江苏南通226200

年份：2007

卷号：14

期号：4

起止页码：268

中文期刊名：药物生物技术

外文期刊名：Pharmaceutical Biotechnology

收录：CSTPCD;;Scopus;CSCD:【CSCD_E2011_2012】；

语种：中文

中文关键词：2’,3'-双脱氧腺苷;胡萝卜软腐欧文氏杆菌;化学酶法;合成;抗病毒

外文关键词：Deoxyadenosine, Erwinia carotovora, Chemo-enzymatic synthesis, Antivirus

摘要：2’,3’-双脱氧腺苷(ddA)具有良好的抗病毒作用。以胸苷为起始原料,经由酰化、环化、开环、催化加氢生成2’,3’-双脱氧胸苷(ddT),然后ddT和腺嘌呤在胡萝卜软腐欧文氏杆菌的作用下转化成胸腺嘧啶和ddA。结果显示在最佳酶反应条件如下:反应温度55℃,磷酸盐缓冲液pH值8.0,磷酸盐缓冲液浓度50 mmol/L,底物20 mmol/L,菌体量10%时,48 h转化率达54.2%。
A new method for the preparation of 2＇,3＇-dideoxyadenosine（ddA）, one of potential antivirus agents, was studied. 2＇, 3＇-dideoxythymidine（ddT） was chemically synthesized from thymidine by the following four steps： alkylation, cyclization, ring cleavage and hydrogenation. The yield of ddT can reach 24.7% based on thymidine. Then ddA was enzymatically transferred from ddT and adenine by using Er＇winia carotovora DOX08 with thymidine phosphorylase and purine nucleoside phosphorylase through the base exchange reaction from 2＇, 3＇-dideoxythymidine and adenine. The optimal enzymatic reaction conditions were studied in 50 ml shaking bottle with 10 ml solution. The experiment showed that the optimum substrate concentration was 20 mmol/L 2＇, 3＇-dideoxythymidine and adenine, 10G wet whole cells and 50 mmol/L pH 8. 0 phosphate buffer. The conversion yield could reach 54.2 G after the reaction solution was incubated at 55℃ for 48 h. ddA acquired in this study was the same as standard ddA sample through NMR detection.