Quantitative structure-activity relationship of prolyl oligopeptidase inhibitory peptides derived from beta-casein using simple amino acid descriptors. 2006

Are Hugo Pripp
Dairy Technology, Department of Food Science, The Royal Veterinary and Agricultural University, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark. ahpr@kvl.dk

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.

UI MeSH Term Description Entries
D007526 Isoelectric Point The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. Isoelectric Points,Point, Isoelectric,Points, Isoelectric
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011392 Proline A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons. L-Proline,L Proline
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D002364 Caseins A mixture of related phosphoproteins occurring in milk and cheese. The group is characterized as one of the most nutritive milk proteins, containing all of the common amino acids and rich in the essential ones. alpha-Casein,gamma-Casein,AD beta-Casein,Acetylated, Dephosphorylated beta-Casein,Casein,Casein A,K-Casein,Sodium Caseinate,alpha(S1)-Casein,alpha(S1)-Casein A,alpha(S1)-Casein B,alpha(S1)-Casein C,alpha(S2)-Casein,alpha-Caseins,beta-Casein,beta-Caseins,epsilon-Casein,gamma-Caseins,kappa-Casein,kappa-Caseins,AD beta Casein,Caseinate, Sodium,K Casein,alpha Casein,alpha Caseins,beta Casein,beta Caseins,beta-Casein Acetylated, Dephosphorylated,beta-Casein, AD,epsilon Casein,gamma Casein,gamma Caseins,kappa Casein,kappa Caseins
D002627 Chemistry, Physical The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes. Physical Chemistry,Chemistries, Physical,Physical Chemistries
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000085822 Prolyl Oligopeptidases A family of serine proteases with specificity for proline-specific cleavage of peptides that are not longer than 30 amino acids. In humans it is broadly distributed in all tissues with higher activity found in the brain. Post-Proline Cleaving Enzyme,Post-Proline Endopeptidase,Proline Endopeptidase,Proline Specific Endopeptidase,Prolyl Endopeptidase,Prolyl Endopeptidase (Thiol-dependent),Prolyl Endopeptidase I,Prolyl Oligopeptidase,Endopeptidase I, Prolyl,Endopeptidase, Post-Proline,Endopeptidase, Proline Specific,Oligopeptidases, Prolyl,Post Proline Cleaving Enzyme,Post Proline Endopeptidase
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein

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