Quantitative structure-activity relationship of prolyl oligopeptidase inhibitory peptides derived from β-casein using simple amino acid descriptors

Quantitative structure-activity relationship (QSAR) modeling using simple amino acid descriptors was done on a set of prolyl oligopeptidase (POP) inhibitory peptides derived from beta-casein. Using partial least-squares regression, a QSAR model was obtained indicating that increased hydrophobicity and molecular bulkiness of amino acids in positions P3, P2, and P1' of inhibitory sites on peptides resulted in increased inhibition (lower IC50). Proline residues were always assumed to be in position P1. Hydrophobicity and molecular bulkiness have also in other studies been found as important factors for binding between substrates (or inhibitors) and the active site of POP. Prolyl oligopeptidase in blood serum is found to influence the level of hormone and neuropeptides and be related to cognitive and neurological deficiencies, e.g., Alzheimer's disease. Increased knowledge of the relationship between peptides derived from food proteins and their POP inhibition may be important in the development of functional foods as a supplement to pharmaceutical agents.