New Chemical Descriptors Relevant for the Design of Biologically Active Peptides. A Multivariate Characterization of 87 Amino Acids
- 4 June 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 41 (14) , 2481-2491
- https://doi.org/10.1021/jm9700575
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Optimization and visualization of molecular diversity of combinatorial librariesMolecular Diversity, 1996
- Quantitative Structure-Property Relationships of Azurin Mutants fromPseudomonas AeruginosaQuantitative Structure-Activity Relationships, 1996
- Quantitative Structure−Activity Relationships of the Synthetic Substrates for Elastase Enzyme Using Nonlinear Partial Least Squares RegressionJournal of Chemical Information and Computer Sciences, 1996
- Pharmacological and Biochemical Profiles of Unique Neurotensin 8-13 Analogs Exhibiting Species Selectivity, Stereoselectivity, and SuperagonismJournal of Biological Chemistry, 1995
- Design and Structure-Activity Relationships of C-Terminal Cyclic Neurotensin Fragment AnalogsJournal of Medicinal Chemistry, 1995
- Theoretical amino acid descriptors. Application to bradykinin potentiating peptidesPeptides, 1991
- Minimum analogue peptide sets (MAPS) for quantitative structure‐activity relationshipsInternational Journal of Peptide and Protein Research, 1991
- Peptide quantitative structure-activity relationships, a multivariate approachJournal of Medicinal Chemistry, 1987
- Deoxyribonucleoside-3′,5′ Cyclic Phosphates. Synthesis and Acid-Catalyzed and Enzymic HydrolysisJournal of the American Chemical Society, 1964
- The Hydrogenation of Ethylene over Copper. I. Reproducing the Activity of the CatalystJournal of the American Chemical Society, 1952