A System for the Study of Kallikreins
The formation of kallidin (lysyl-bradykinin) by the action of glandular kallikreins upon plasma kininogen shows that the substrate specificity of these enzymes is very different from that of trypsin and plasma kallikrein, which yield bradykinin from the same substrate. Although one of the bonds cleaved by glandular kallikrein (Arg-Ser, at the carboxyl end of bradykinin and kallidin) is a typical trypsin substrate cleavage site, and is also cleaved by plasma kallikrein, the other site (Met-Lys, at the amino end of kallidin) is not cleaved by trypsin and plasma kallikrein. This unique second cleavage site has led to considerable work and discussion as to whether the enzyme has one or two active sites (see Fiedler and Leysath, and Prado and Araujo-Viel, this volume). In order to study glandular kallikreins more exactly and as an aid to development of specific inhibitors for glandular kallikreins, a new set of substrates has been synthesized and used for initial studies with rat urinary kallikrein (RUK).
KeywordsHigh Pressure Liquid Chromatography Active Kinin Amidase Activity Chloromethyl Ketone Plasma Kallikrein
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- Amundsen, E., L. Svendsen, A.M. Vennerod and K. Laake, 1976. Determination of Plasma Kallikrein with a new Chromogenic Tripeptide Derivative, in: Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease, ed. J.J. Pisano (US Government Printing Office Publication (NIH)76–791) p. 215.Google Scholar
- Freer, R.J., and J.M. Stewart, 1972. Alkylating Analogs of Peptide Hormones. I. Synthesis and Properties of Chlorambucil Derivatives of Bradykinin and Bradykinin Potentiating Factor. J. Med. Chem. 15: 1.Google Scholar
- Kato, H., Y.N. Han and S. Iwanaga, 1977. Primary Structure of Bovine Plasma Low-Molecular Weight Kininogen, J. Biochem. ( Tokyo ) 82: 377.Google Scholar
- Morris, D.H., and J.M. Stewart, 1979. A New Assay for Urinary Kallikrein, in: Current Concepts in Kinin Research, ed. G.L. Haberland (Pergamon, Oxford) in press.Google Scholar
- Silva, E., C.R. Diniz and M. Mares-Guia, 1974. Rat Urinary Kallikrein: Purification and Properties, Biochemistry 13: 4304.Google Scholar