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 phys icochemical descriptor variables. These descriptor variables include e xperimentally determined retention values in seven thin-layer chromato graphy !TLC) systems, three nuclear magnetic resonance (NMR) shift var iables, and 16 calculated variables, namely six semiempirical molecula r orbital indices, total, polar, and nonpolar surface area, van der Wa als volume of the side chain, log P, molecular weight, and four indica tor 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 wit h 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 ex tended and updated principal property scales, the z-scales, were calcu lated and aligned to previously reported z(old)-scales. The appropriat eness of the extended z-scales were validated by the use in quantitati ve sequence-activity modeling (QSAM) of 89 elastase substrate analogue s and in a QSAM of 29 neurotensin analogues.