物理化学学报 >> 1998, Vol. 14 >> Issue (10): 893-897.doi: 10.3866/PKU.WHXB19981007

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磷脂酶A2吲哚类抑制剂的结构和活性关系

王任小, 冯亚彬, 来鲁华, 唐有祺   

  1. 北京大学物理化学研究所，北京 100871
  • 收稿日期:1997-12-24 修回日期:1998-04-20 发布日期:1998-10-15
  • 通讯作者:

Structure-Affinity Relationship of lndole-Based for Phospholipase A2

Wang Ren-Xiao, Feng Ya-Bin, Lai Lu-Hua, Tang You-Qi   

  1. Institute of Physical Chemistry,Peking University,Beijing 100871
  • Received:1997-12-24 Revised:1998-04-20 Published:1998-10-15
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摘要：

 应用一种新的预测酶-配体复合物亲和性的方法来研究磷脂酶A2吲哚类抑制剂的结构-活性关系．磷脂酶A2-抑制剂复合物的三维结构是用分子模构的方法搭建的，复合物的亲和性由程序SCORE计算．共分析了12个抑制剂分子．计算所得的亲和性和实验测定值吻合得很好，明显优于用CoMFA方法分析同一系列化合物所给出的结果．通过分析SCORE的输出结果，识别出了吲哚类抑制剂和磷脂酶A2相互作用的关键位点，为设计新型的磷脂酶A2抑制剂提供了指导．

关键词: 凝酯酶A2, 吲哚类抑制剂, 基于结构的定量构效关系, 药物设计

Abstract:

 A new method which can estimate the binding affinity of an enzyme-ligand complex was applied to studying the indole-based inhibitors for human synovial fluid phospholipase A2.The three-dimensional structures of phospholipase-inhibitor complexes were modeled by molecular docking and energy minimization. The bindmg affinities were calculated by program SCORE. All together 12 inhibitors were analyzed .The calc The calculated IC50 values fit well with the experimentally observed values By contrast, CoMFA studies of the same series of inhibitors yielded much poorer results. From SCORE's output, the pharmacophorc of phospholipase A2 inhibitors was also derived, which is valuable for designing novel inhibitors.

Key words: Phospholipase A2, Indole-based inhibitors, Structure-based quantittive structure activity relationship, Drug design