物理化学学报 >> 1997, Vol. 13 >> Issue (12): 1090-1096.doi: 10.3866/PKU.WHXB19971207

研究论文 上一篇    下一篇

促生长激素释放素三维定量构效关系及药效团模型

刘亮,王任小,来鲁华,李崇熙   

  1. 北京大学化学与分子工程学院，北京 100871
  • 收稿日期:1997-03-18 修回日期:1997-05-28 发布日期:1997-12-15
  • 通讯作者: 来鲁华

3D-QSAR and Pharmacophore Modeling of Growth Hormone Secretagogues

Liu Liang,Wang Ren-Xiao,Lai Lu-Hua,Li Chong-Xi   

  1. College of Chemistry and Molecular Engineering,Peking University,Beijing 100871
  • Received:1997-03-18 Revised:1997-05-28 Published:1997-12-15
  • Contact: Lai Lu-Hua

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摘要：

用比较分子场分析（CoMFA）方法对促生长激素释放素L-692，429的系列物进行了三维定量构效研究. 得到具有较强预测能力的模型并确定了母体的活性构象. 用距离比较方法将L-692，429的活性构象与两个活性多肽进行了迭合，找到了可能的药效团. 药效团模型显示L-692,429的氨基和四唑是氢键的给体和受体，而A和C环是主要的疏水核心.

关键词: 促生长激素释放素, CoMFA, DISCO, 药效团, 多肽类似物

Abstract:

Comparative molecular field analysis (CoMFA) was applied to the quantitative structure-activity relationship studies of growth hormone secretagogues. The final model is highly predictive, and the active conformation of this series of compounds was derived based on the model. This speculated active conformation was then imposed on the conformations of two known bioactive peptides by distance-comparision (DISCO) analysis to find a reasonable pharmacophore. It was shown that the amino group on L-692, 429 is a hydrogen bond donor while the tetrazole ring is a hydrogen bond acceptor, and, A ring and C ring are main hydrophobic cores.

Key words: Growth hormone secretagogue, CoMFA, DISCO, Pharmacophore, Peptide mimetics