Quantitative Structure−Activity Relationship of Prolyl Oligopeptidase Inhibitory Peptides Derived from β-Casein Using Simple Amino Acid Descriptors

• Published in: Journal of agricultural and food chemistry Vol. 54; no. 1; pp. 224 - 228
• Main Author: Pripp, Are Hugo
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 11.01.2006
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; beta-casein; Binding Sites; Biological and medical sciences; casein hydrolysates; Caseins - chemistry; Chemical Phenomena; Chemistry, Physical; enzyme inhibitors; Food industries; functional foods; Fundamental and applied biological sciences. Psychology; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; hydrophobicity; Isoelectric Point; medicinal properties; Milk and cheese industries. Ice creams; molecular bulkiness; neurophysiology; peptidases; peptides; Peptides - chemistry; Peptides - pharmacology; Proline - chemistry; prolyl oligopeptidase; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Quantitative Structure-Activity Relationship; quantitative structure-activity relationships; Regression Analysis; Serine Endopeptidases - blood; Serine endopeptidases; Peptides; Enzyme; Prolyl oligopeptidase; Dairy product; POP; Peptidases; Milk protein; Acids; Casein; Structure activity relation; Hydrolases; Descriptor; PEP; Milk
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf0521303

Quantitative structure−activity relationship (QSAR) modeling using simple amino acid descriptors was done on a set of prolyl oligopeptidase (POP) inhibitory peptides derived from β-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. Keywords: Milk; casein; prolyl oligopeptidase; PEP; POP