摘要
过氧化物酶体增殖因子活化受体 (PPAR)是核受体超家族的一员 .基于受体结构的药物分子设计与组合化学策略相结合 ,构建了过氧化物酶体增殖因子活化受体 (PPAR)激动剂的虚拟化合物库 .将已知小分子配体 (GW40 95 44 )与PPAR晶体复合物进行剥离 ,得到受体的活性构象 ,并利用此活性受体分子与虚拟库中小分子进行对接和虚拟筛选 ,得到理论上结合较强的化合物 ,并对这些化合物进行合成 ,共合成 9个新化合物 .活性筛选结果显示化合物对PPAR具有一定的亲和力 ,其中有三个化合物显示出对PPARα ,PPARγ的双重激动作用 。
The PPARs are members of the nuclear hormone receptor super family. A novel virtual library of PPAR agonists by structure-based drug design and combinatorial library method was described. The PPAR-LBD 3D model used for virtual screening was built by the 1K74 and 1K71 crystal structure. After DOCK program screening, which automatically simulated the interaction between the ligands and receptors, the strong-binding virtual compounds were selected and synthesized. Nine new compounds have been synthesized. Three of them exhibitpotent dual PPARalpha/gamma agonist activity as demonstrated by in vitro binding. The activity data offered detailed molecular information for design and synthesis of new compounds.
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2004年第16期1544-1550,共7页
Acta Chimica Sinica
基金
北京市自然科学基金 (No.70 2 2 0 2 6)
教育部博士点基金 (No.2 0 0 2 0 0 2 30 32 )资助项目
