Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of 38 rubiscolins as ? opioid peptides using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 30 peptides. The best CoMFA model included electrostatic and steric fields and had a moderate Q 2 = 0.503. CoMSIA analysis surpassed the CoMFA results: the best CoMSIA model included only the hydrophobic field and had a Q 2 = 0.661. In addition, this model predicted adequately the peptides contained in the test set. Our model identified that the potency of ? opioid activity of rubiscolin analogues essentially exhibited a significant relationship with local hydrophobic and hydrophilic characteristics of amino acids at positions 3, 4, 5, and 6. © 2007 American Chemical Society.