부산대학교 도서관

A gradual truncation of the primary structure of frog skin-derived Huia versabilis Bowman-Birk peptidic inhibitor (HV-BBI) resulted in 18-times stronger inhibitor of matriptase-1 (peptide 6 , K i = 8 n m) in comparison to the full-length HV-BBI (K i = 155 n m). Analogous increase in the inhibitory activity in correlation with the peptide length reduction was not observed in case of other serine proteases, bovine trypsin (K i = 151 n m for peptide 6 and K i = 120 n m for HV-BBI) and plasmin (K i = 120 n m for peptide 6 and 82 n m for HV-BBI). Weaker binding affinity to these enzymes emphasized an inhibitory specificity of peptide 6. Molecular dynamic analysis revealed that the observed variations in the binding affinity of peptide 6 and HV-BBI with matriptase-1 are associated with the entropic differences of the unbound peptides. Moreover, several aspects explaining differences in the inhibition of matriptase-1 by peptide 6 (bearing the C -terminal amide group) and its two analogues, peptide 6∗ (having the C -terminal carboxyl group, K i = 473 n m) and cyclic peptide 6∗∗ (K i = 533 n m), both exhibiting more than 50-fold reduced inhibitory potency, were discovered. It was also shown that peptide 6 presented significantly higher resistance to proteolytic degradation in human serum than HV-BBI. Additional investigations revealed that, in contrast to some amphibian-derived inhibitors, HV-BBI and its truncated analogues do not possess bactericidal activity, thus they cannot be considered as bifunctional agents. Image 1 • Truncated analogue of frog-derived peptide inhibitor binds strongly to matriptase-1. • The truncated peptide is 18-times stronger inhibitor of matriptase-1 than native one. • Such binding variations are associated with the entropic differences of the unbound peptides. • The truncated peptide is significantly more resistant to proteolysis in human serum. • Interaction between its C -terminal amide and enzyme Phe explains inhibitory potency. [ABSTRACT FROM AUTHOR]