Quantitative structure-activity relationship study of bitter di- and tri-peptides including relationship with angiotensin I-converting enzyme inhibitory activity



Bitterness represents a major challenge in industrial application of food protein hydrolysates or bioactive peptides and is a major factor that controls the flavor of formulated therapeutic products. The aim of this work was to apply quantitative structure-activity relationship modeling as a tool to determine the type and position of amino acids that contribute to bitterness of di- and tri-peptides. Datasets of bitter di- and tri-peptides were constructed using values from available literature, followed by modeling using partial least square (PLS) regression based on the three z-scores of 20 coded amino acids. Prediction models were validated using cross-validation and permutation tests. Results showed that a single-component model could explain 52 and 50% of the Y variance (bitterness threshold) of bitter di- and tri-peptides, respectively. Using PLS regression coefficients, it was determined that hydrophobic amino acids at the carboxyl-terminus and bulky amino acid residues adjacent to the carboxyl terminal are the major determinants of the intensity of bitterness of di- and tri-peptides. However, there was no significant (p > 0.05) correlation between bitterness of di- and tri-peptides and their angiotensin I-converting enzyme-inhibitory properties. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.