New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids.

In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical descriptor variables. These descriptor variables include experimentally determined retention values in seven thin-layer chromatography (TLC) systems, three nuclear magnetic resonance (NMR) shift variables, and 16 calculated variables, namely six semiempirical molecular orbital indices, total, polar, and nonpolar surface area, van der Waals volume of the side chain, log P, molecular weight, and four indicator variables describing hydrogen bond donor and acceptor properties, and side chain charge. In the present study, the data from a previous characterization of 55 AA.s from our laboratory have been extended with data for 32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected to represent both intermediate and more extreme physicochemical properties, compared to the 20 coded AA.s. The new extended and updated principal property scales, the z-scales, were calculated and aligned to previously reported z(old)-scales. The appropriateness of the extended z-scales were validated by the use in quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues and in a QSAM of 29 neurotensin analogues.