Human mast cell tryptase

Tryptase is at the present moment the main clinical marker for anaphylaxis and mastocytosis. There are two major human mast cells tryptases, a- and (3-tryptase, encoded by two genes located at chromosome 16. The haploid genotype for tryptase is (3a or (3(3.25% of individuals are a-tryptase-deficient a-tryptase shows a 90% amino acid sequence identity with (3-tryptase. 

Schwartz LB, Yunginger JW, Miller J, Bokhari R, Dull D Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 1989 83 1551-1555. 

Inhibitors Against Human Mast Cell Tryptase ... 

I 3.2 Inhibitors Against Human Mast Cell Tryptase A Potential Approach to Attack Asthma ... 

The in-vitro inhibition activity of the synthesized target compounds against human mast cell tryptase is summarized in Tables 3.2.1 and 3.2.2 Compound 8, which contains aminomethyl benzyl moieties as head groups, was the most potent of the pyran series (type I), with a Ki value of 1.3 nM. Compared with 8, the tryptase inhibitors with aminomethylcyclohexyl substituents (17, 18, and 21), were 100-fold (Ki = 130 nM), 60-fold (Ki = 75 nM), and approximately 90-fold (Ki = 120 nM) less... 

Inhibitors Against Human Mast Cell Tryptase A Potential Approach to Attack Asthma Tab. 3.2.1. The synthesized type II target inhibitors 9, and 24-29, and their K values. 

Heparin has been used in enzyme purification such as recombinant human mast cell tryptase. The purified enzyme is fully active [12]. Heparin-based affinity chromatography also permitted the isolation of growth factors such as basic fibroblast growth factor (bFGF). The affinity is lower when bFGF is complexed with acidic gelatin [13]. The elution of synthetic TFPI (tissue factor pathway inhibitor) peptidic fragments on immobilized heparin has allowed one to find the peptidic sequence responsible for the TFPI-heparin interaction [14]. 

Alter, S.C., Kramps, J.A., Janoff, A. and Schwartz, L.B. (1990). Interactions of human mast cell tryptase with biological protease inhibitors. Arch. Biochem. Biophys. 276, 26-31. 

Gruber, B.L., Marchese, M.J., Suzuki, K., Schwartz, L.B., Okada, Y., Nagese, H. and Ramamurthy, N.S. (1989). Synovial procollagenase activation by human mast cell tryptase dependance upon matrix metalloproteinase 3 activation. J. Clin. Invest. 84, 1657-1662. 

Lohi, J., Harvima, I. and Keski-Oja, J. (1992). Pericellular substrates of human mast cell tryptase 72,000 Dalton gelatinase and fibronectin. J. Cell. Biochem. 50, 337-349. 

Schwartz, L.B., Bradford, T.R, Lee, D.C. and Chlebowski, J.F. (1990). Immunologic and physicochemical evidence for conformational changes occurring on conversion of human mast cell tryptase from active tetramer to inactive monomer. Production of monoclonal antibodies recognizing active tryptase. J. Immunol. 144, 2304—2311. 

Walls, A.F., Bennett, A.R, McBride, H.M., Glennie, M.J., Holgate, S.T. and Church, M.K. (1990a). Production and characterization of monoclonal antibodies specific for human mast cell tryptase. Clin. Exp. Allergy 20, 581-589. 

Walls, A.F., Brain, S.D., Desai, A., Jose, P.J., Hawkings, E., Church, M.K. and Williams, T.J. (1992b). Human mast cell tryptase attenuates the vasodilator activity of calcitonin gene-related peptide. Biochem. Pharmacol. 43, 1243-1248. 

Schwartz LB, Kawahara MS, Hugh TE, Vik D, Fearon DT, Austen KF Generation of C3a anaphy-latoxin from human C3 by human mast cell tryptase. J Immunol 1983 130 1891-1895. 

WALLS, A.F., HE, S TERAN, L BUCKLEY, M.G., KI-SUCK, J HOLGATE, S.T., SHUTE. J.K. CAIRNS, J.A. (1995) Granulocyte recruitment by human mast cell tryptase. International Archives of Allergy and Immunology, 107, 372-373. 

Spirocyclic piperidine amides as potent, nonpeptide inhibitors of human mast cell tryptase... 

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