Principal property values for six non-natural amino acids and their application to a structure–activity relationship for oxytocin peptide analogues

Abstract

Previously derived principal property scales for the 20 coded amino acids have been extended to six noncoded amino acids, namely ornithine, norvaline, norleucine, O-methylated threonine, α-amino butyric acid, and citrulline. This has been done first, for the 20 coded amino acids, by developing PLS models for the relations between the previously derived scales (z1, z2, and z3) and newly measured thin-layer chromatography data, proton nuclear magnetic resonance data, plus literature data describing amino acid "bulk" (van der Waals volume and molecular mass). Thereafter, z values for the noncoded amino acids were calculated by inserting the same measured data for these compounds into the PLS models. As a validation, the calculated z values were then used to describe the structural variation of a set of 60 oxytocin peptide analogues for which literature data on biological measurements existed. The models explain 71–81% of the variance of the biological data and are highly significant according to cross-validation. Prediction errors of about twice the estimated biological measurement error are obtained for the 11 peptide analogues containing noncoded amino acids.