聚腺苷二磷酸核糖聚合酶-1抑制剂高通量筛选模型  

HTS model for Poly(ADP-ribose) polymerase-1 inhibitors

作　　者：柳军[1] 张陆勇[1] 

机构地区：[1]中国药科大学新药筛选中心,南京江苏210009

出　　处：《中国药理学通报》2007年第1期124-127,共4页Chinese Pharmacological Bulletin

基　　金：国家高技术研究发展计划(863计划)新型高通量筛选模型;化合物库建设和药物筛选"十五"重大科技专项资助项目(No2004AA234011);新世纪优秀人才支持计划资助项目(NoNCET-04-0507)

摘　　要：目的建立体外聚腺苷二磷酸核糖聚合酶-1[Poly(ADP-ribose)polymerase-1,PARP-1]抑制剂的高通量筛选模型,筛选潜在的PARP-1抑制剂。方法将PARP-1、裸DNA与底物NAD+反应,再将剩余底物NAD+转化为荧光物质,通过测定其荧光强度来决定PARP-1的活性,并以此筛选PARP-1的抑制剂。建立384孔板的高通量筛选模型,对9280个化合物(包括合成化合物、天然产物、微生物发酵提取物)组成的随机库进行体外筛选。结果筛选出148个活性化合物对PARP-1的抑制作用大于70%,最终确定3个化合物具有较高的抑制活性。结论建立的PARP-1抑制剂高通量筛选模型具有灵敏度高、快速、微量、准确的特点。Aim To introduce a high throughput screen model for PARP-1 inhibitors. Methods Setting up an assay for PARP-1 activity relies on the conversion of NAD^＋ into a highly fluorescent compound. The inhibitory effects of 9 280 samples （ including pure organic compounds, extracts from plants and extracts from microorganism）were screened by the high throughout assay. Results 148 compounds had inhibitory effects over 70%. Ultimately, three inhibitors were identified as PARP-1 inhibitor with high activity. Conclusion The high throughput screening was a highly sensitive, inexpensive, and operationally simple assay method in identifying PARP-1 inhibitors.

关 键 词：PARP-1 抑制剂 高通量筛选 

分 类 号：R-332[医药卫生] R345.57