OCTANOL-WATER PARTITION OF NONZWITTERIONIC PEPTIDES - PREDICTIVE POWER OF A MOLECULAR SIZE-BASED MODEL

A remarkably simple, molecular size-based model developed to predict o ctanol-water partition coefficients or organic compounds is tested on a set of 188 neutral peptides with available experimental partition da ta, Despite using only two parameters, it gives a promising correlatio n (r(2) = 0.914; sigma = 0.455, F = 1978.0), and predictions are in a realistic range even for larger peptides (cyclosporin, melanotan, sand ostatin) where common, overparametrized fragment methods become quite unreliable, Ion-pah partitioning and the extraction constant formalism is briefly reviewed to describe the sigmoidal lipophilicity profile o f ionizable, nonzwitterionic peptides, It seems possible to extend the present model to estimate apparent partition coefficients measured ar ound neutral pH and physiological conditions for monoionic peptides; h owever, as no standard conditions are yet defined. and only relatively small number of experimental data are available, the situation here i s more complex. (C) 1998 Wiley-Liss, Inc.