757. Aprotinin

Nomenclature

CAS number: 9087-70-1
Pancreatic basic trypsin inhibitor; pancreatic trypsin inhibitor (Kunitz); Bayer A 128; Riker 52G; RP-9921; Antagosan (HMR); Antikrein (Teikoku Zoki); Fosten (Serono); Iniprol (Sanofi Winthrop); Kir Richter (Lepetit); Repulson (Mochida); Trasylol (Bayer); Trazinin (Tobishi); Zymofren (Specia).
C284H432N84O79S7; mol wt 6511.44.
C 52.39%, H 6.69%, N 18.07%, O 19.41%, S 3.45%.

Description and references

Serine protease inhibitor which inhibits kallikrein, plasmin, trypsin, chymotrypsin and various intracellular proteases. Single chain polypeptide containing 58 amino acids; found in tissues and blood, highest concentration in bovine parotid gland, pancreas and lung. Initial description: H. Kraut et al., Z. Physiol. Chem. 192, 1 (1930). Isoln from bovine pancreas: M. Kunitz, J. H. Northrup, J. Gen. Physiol. 19, 991 (1936); from bovine parotid glands: H. Kraut, R. Krbel, US 2890986 (1959 to Bayer). Amino acid sequence: B. Kassell et al., Biochem. Biophys. Res. Commun. 18, 255 (1965); F. A. Anderer, S. Hrnle, Z. Naturforsch. 20b, 457, 462 (1965); B. Kassell, M. Laskowski, Biochem. Biophys. Res. Commun. 20, 463 (1966). Two-dimensional 1H-NMR studies: K. Nagayama, K. Wüthrich, Eur. J. Biochem. 114, 365 (1981); G. Wagner et al., ibid. 375. Review of early literature: I. Trautschold et al., Biochem. Pharmacol. 16, 59-72 (1957). Review of mechanism of therapeutic action: G. Haberland, R. McConn, Fed. Proc. 38, 2760-2767 (1979). Review of use as a proteolytic inhibitor in radioimmunoassays of polypeptide hormones: E. S. Zyzner, Life Sci. 28, 1861-1866 (1981). Review of biochemistry and applications: H. Fritz, G. Wunderer, Arzneim.-Forsch. 33, 479-494 (1983); of pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery: R. Davis, R. Whittington, Drugs 49, 954-983 (1995).

Chemical structure

Properties

uv max (pH 5.9): 280 nm. Isoelec pt pH 10.5. Stable in neutral or acid media at high temp. Irreversible changes in molecular structure occur in strongly alkaline media (pH >12). Partially and reversibly denatured on treatment with 8M urea. May be kept at room temp in physiological saline soln for >1 yr without detrimental effects. LD50 i.v. in mice: 2500000 kallikrein inhibitor units/kg (Trautschold).

Use

Proteolytic inhibitor in radioimmunoassays of polypeptide hormones.

Therapeutic Category

Protease inhibitor.

Keywords

Protease Inhibitor