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. 1983 Aug;49(4):685–691.

New synthetic inhibitor to the alternative complement pathway.

N Ikari, Y Sakai, Y Hitomi, S Fujii
PMCID: PMC1454324  PMID: 6553561

Abstract

The inhibitory effects of 6-amidino-2-naphthyl 4-guanidinobenzoate (FUT-175) on the activities of factor B, factor D and cobra venom factor (CVF) X Bb were examined. FUT-175 bound specifically to the Bb fragment of factor B or CVF X Bb. FUT-175 was a non-competitive inhibitor of the esterolysis of L-leucyl-L-alanyl-L-arginine naphthylester by factor B and CVF X Bb. FUT-175 also inhibited the haemolytic activity of factor B, the C3 convertase activity of CVF X Bb and the factor B-cleaving activity of factor D. The concentration of FUT-175 causing 50% inhibition of these activities was 10(-5) - 10(-4)M.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Caporale L. H. Leupeptin inhibits the C3/5 convertase CVFBb of the complement system. Biochim Biophys Acta. 1981 Jul 24;660(1):151–153. doi: 10.1016/0005-2744(81)90121-2. [DOI] [PubMed] [Google Scholar]
  2. Christie D. L., Gagnon J., Porter R. R. Partial sequence of human complement component factor B: novel type of serine protease. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4923–4927. doi: 10.1073/pnas.77.8.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooper N. R. Formation and function of a complex of the C3 proactivator with a protein from cobra venom. J Exp Med. 1973 Feb 1;137(2):451–460. doi: 10.1084/jem.137.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dieminger L., Vogt W., Lynen R. Purification and some properties of factor D of the human properdin system. Z Immunitatsforsch Immunobiol. 1976 Nov;152(3):231–243. [PubMed] [Google Scholar]
  5. Fearon D. T., Austen K. F., Ruddy S. Properdin factor D: characterization of its active site and isolation of the precursor form. J Exp Med. 1974 Feb 1;139(2):355–366. doi: 10.1084/jem.139.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujii S., Hitomi Y. New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta. 1981 Oct 13;661(2):342–345. doi: 10.1016/0005-2744(81)90023-1. [DOI] [PubMed] [Google Scholar]
  7. Ikari N., Hitomi Y., Niinobe M., Fujii S. Studies on esterolytic activity of alternative complement component factor B. Biochim Biophys Acta. 1983 Jan 26;742(2):318–323. doi: 10.1016/0167-4838(83)90317-5. [DOI] [PubMed] [Google Scholar]
  8. Ikari N., Niinobe M., Fujii S. Proteolysis of factor B by plasma kallikrein and plasmin. FEBS Lett. 1981 Aug 17;131(1):143–146. doi: 10.1016/0014-5793(81)80906-4. [DOI] [PubMed] [Google Scholar]
  9. Janatova J., Lorenz P. E., Schechter A. N., Prahl J. W., Tack B. F. Third component of human complement: appearance of a sulfhydryl group following chemical or enzymatic inactivation. Biochemistry. 1980 Sep 16;19(19):4471–4478. [PubMed] [Google Scholar]
  10. Lesavre P. H., Hugli T. E., Esser A. F., Müller-Eberhard H. J. The alternative pathway C3/C5 convertase: chemical basis of factor B activation. J Immunol. 1979 Aug;123(2):529–534. [PubMed] [Google Scholar]
  11. Medicus R. G., Götze O., Müller-Eberhard H. J. The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol. 1976;5(9):1049–1055. doi: 10.1111/j.1365-3083.1976.tb03056.x. [DOI] [PubMed] [Google Scholar]
  12. Mole J. E., Niemann M. A. Structural evidence that complement factor B constitutes a novel class of serine protease. J Biol Chem. 1980 Sep 25;255(18):8472–8476. [PubMed] [Google Scholar]
  13. Pepys M. B., Tompkins C., Smith A. D. An improved method for the isolation from Naja naja venom of cobra factor (CoF) free of phospholipase A. J Immunol Methods. 1979;30(2):105–117. doi: 10.1016/0022-1759(79)90085-1. [DOI] [PubMed] [Google Scholar]
  14. Platts-Mills T. A., Ishizaka K. Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974 Jul;113(1):348–358. [PubMed] [Google Scholar]
  15. Tack B. D., Prahl J. W. Third component of human complement: purification from plasma and physicochemical characterization. Biochemistry. 1976 Oct 5;15(20):4513–4521. doi: 10.1021/bi00665a028. [DOI] [PubMed] [Google Scholar]
  16. Takada Y., Arimoto Y., Mineda H., Takada A. Inhibition of the classical and alternative pathways by amino acids and their derivatives. Immunology. 1978 Mar;34(3):509–515. [PMC free article] [PubMed] [Google Scholar]
  17. Vogt W., Dames W., Schmidt G., Dieminger L. Complement activation by the properdin system: formation of a stoichiometric. C3 cleaving complex of properdin factor B with C36. Immunochemistry. 1977 Mar;14(3):201–205. doi: 10.1016/0019-2791(77)90195-1. [DOI] [PubMed] [Google Scholar]
  18. Vogt W., Dieminger L., Lynen R., Schmidt G. Alternative pathway for the activation of complement in human serum. Formation and composition of the complex with cobra venom factor that cleaves the third component of complement. Hoppe Seylers Z Physiol Chem. 1974 Feb;355(2):171–183. doi: 10.1515/bchm2.1974.355.1.171. [DOI] [PubMed] [Google Scholar]

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