title: Peptide modulators of alpha-glucosidase.
abstract: OBJECTIVE
  Acute glucose fluctuations during the postprandial period pose great risk for cardiovascular complications and thus represent an important therapeutic approach in type 2 diabetes. In the present study, screening of peptide libraries was used to select peptides with an affinity towards mammalian intestinal alpha-glucosidase as potential leads in antidiabetic agent development.
  
  
  METHODS
  Three phage-displayed peptide libraries were used in independent selections with different elution strategies to isolate target-binding peptides. Selected peptides displayed on phage were tested to compete for an enzyme-binding site with known competitive inhibitors, acarbose and voglibose. The four best performing peptides were synthesized. Their binding to the mammalian alpha-glucosidase and their effect on enzyme activity were evaluated.
  
  
  RESULTS
  Two linear and two cyclic heptapeptides with high affinity towards intestinal alpha-glucosidase were selected. Phage-displayed as well as synthetic peptides bind into or to the vicinity of the active site on the enzyme. Both cyclic peptides inhibited enzyme activity, whereas both linear peptides increased enzyme activity.
  
  
  CONCLUSIONS
  Although natural substrates of glycosidase are polysaccharides, in the present study we successfully isolated novel peptide modulators of alpha-glucosidase. Modulatory activity of selected peptides could be further optimized through peptidomimetic design. They represent promising leads for development of efficient alpha-glucosidase inhibitors.
authors.affiliation: Entrapharm d.o.o., University of Ljubljana Ljubljana, Slovenia.
authors.forename: Irena
authors.initials: I
authors.lastname: Roskar
authors.affiliation: Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Molek
authors.affiliation: Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana Ljubljana, Slovenia.
authors.forename: Miha
authors.initials: M
authors.lastname: Vodnik
authors.affiliation: Entrapharm d.o.o., University of Ljubljana Ljubljana, Slovenia.
authors.forename: Mateja
authors.initials: M
authors.lastname: Stempelj
authors.affiliation: Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana Ljubljana, Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Strukelj
authors.affiliation: Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
keywords: Maltase glucoamylase; Peptide modulators; Phage display