Predicting the kinetics of peptide-antibody interactions using a multivariate experimental design of sequence and chemical space

A multivariate approach involving modifications in peptide sequence and che mical buffer medium was used as an attempt to predict the kinetics of pepti de-antibody interactions. Using a BIACORE(R) system the kinetic parameters of the interaction of Fab 57P with 18 peptide analogues of an epitope of to bacco mosaic virus protein were characterized in 20 buffers of various pH v alues and containing different chemical additives (NaCl, urea, EDTA, KSCN a nd DMSO), For multivariate peptide design, three amino acid positions were selected because their modification was known to moderately affect binding, without abolishing it entirely. Predictive mathematical models were develo ped which related kinetic parameters (k(a) or k(d)) measured in standard bu ffer to the amino acid sequence of the antigen. ZZ-scales and a helix-formi ng-tendency (HFT) scale were used as descriptors of the physico-chemical pr operties of amino acids in the peptide antigen. These mathematical models h ad good predictive power (Q(2) = 0.49 for k(a), Q(2) = 0.73 for k(d)). For the non-essential residues under study, HFT and charge were found to be the most important factors that influenced the activity. Experiments in 19 buf fers were performed to assess the sensitivity of the interactions to buffer composition. The presence of urea, DMSO and NaCl in the buffer influenced binding properties, while change in pH and the presence of EDTA and KSCN ha d no effect. The chemical sensitivity fingerprints were different for the v arious peptides, The results indicate that multivariate experimental design and mathematical modeling can be applied to the prediction of interaction kinetics. Copyright (C) 2001 John Wiley & Sons, Ltd.