μ-芋螺毒素及其类似物的定量构效关系研究

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

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（PartialLeastSquare）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．

The μ-conotoxins block ion flux through voltage-dependent sodium channelsin skeletal and in electric organs with high selectivity. We have studied the quantitativestructure-activity relationships and developed a QSAR model of μ- conotoxin and its 17derivatives by means of the descriptor scales Z1, Z2, and Z3 and the multivariate dataanalytical method PLS (Partial Least Squares in latent variable). The cross-validated R2of 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 beof 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.