物理化学学报 >> 1996, Vol. 12 >> Issue (06): 485-490.doi: 10.3866/PKU.WHXB19960602

研究论文 上一篇    下一篇

μ-芋螺毒素及其类似物的定量构效关系研究

丁晓琴,陈常英,李玉林,陈冀胜,罗宇,来鲁华,徐筱杰   

  1. 北京药物化学研究所,北京 102205|北京大学物理化学研究所,北京 100871
  • 收稿日期:1995-04-18 修回日期:1996-01-15 发布日期:1996-06-15
  • 通讯作者: 丁晓琴

Quantitative Structure-activity Relationships for μ-conotoxin GIIIA and its Derivatives

Ding Xiao-Qin,Chen Chang-Ying,Li Yu-Lin,Chen Ji-Sheng,Luo Yu,Lai Lu-Hua,Xu Xiao-Jie   

  1. Peking Institute of Pharmaceutical Chemistry,Beijing 102205|Institute of Physical Chemistry,Peking University, 100871
  • Received:1995-04-18 Revised:1996-01-15 Published:1996-06-15
  • Contact: Ding Xiao-Qin

摘要:

μ-芋螺毒素是肌肉型钠离子通道的专一性阻断剂,本文主要采用PLS(Partial Least Square)多元数学分析方法对μ-芋螺毒素及其17个类似物进行了定量构效关系研究,建立了QSAR模型,其模型的交叉验证值R2=0.813,Y实验值与Y预测值的相关系数0.903.计算结果表明,对分子活性影响比较大的是13位精氨酸残基和分子中的电荷变化,增加分子的正电荷,将提高分子的活性,其次是19,2,12,9,和17位氨基酸残基.

关键词: μ-芋螺毒素, PLS, QSAR, 钠离子通道, 多肽

Abstract:

The μ-conotoxins block ion flux through voltage-dependent sodium channels in skeletal and in electric organs with high selectivity. We have studied the quantitative structure-activity relationships and developed a QSAR model of μ- conotoxin and its 17 derivatives by means of the descriptor scales Z1, Z2, and Z3 and the multivariate data analytical method PLS (Partial Least Squares in latent variable). The cross-validated R2 of the QSAR model is 0.813 and the correlation coefficient of yexp. and ypre. is 0.903. The QSARs indicate that 6 different amino acid positions (13, 19, 2, l2, 9, 17) may be of importance, where the guanidine group in the position No.13 and the large number ofpositive charges may be of great importance in the contribution to the activity.

Key words: μ-conotoxin, PLS, QSAR, Sodium Channel, Polypeptide