Inhibition of Porcine Glandular Kallikreins by Structurally Homologous Proteinase Inhibitors of the Kunitz (Trasylol) Type. Significance of the Basic Nature of Amino Acid Residues in Subside Positions for Kallikrein Inhibition

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Abstract
The newly synthesized chromogenic substrate DValLeuArgNHNp was employed to study the inhibition strength of Trasylol-like inhibitors from bovine lung (TKI), sea anemone [Anemonia sulcata] (SAI), snake venoms (NNV [Naja nivea] and HHV [Hemachatus haemachatus]), snails [Helix pomatia] (HPI) and cow colostrum (CTI) against procine pancreatic, submandibular and urinary kallikreins. The dissociation constants of the corresponding kallikrein-inhibitor complexes were found close to Ki = 1.5 .times. 10-9 M (TKI, SAI, NNV) or to Ki = 10-210 .times. 10-9 M (HHV, HPI). CTI did not inhibit the 3 porcine glandular kallikreins. Comparison of the inhibitory active areas of the inhibitors with their affinities to the 3 kallikreins shows that kallikrein inhibition is observed only if basic amino acid residues are present in distinct positions of the inhibitory active sites.