Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Dec 15;256(3):989–994. doi: 10.1042/bj2560989

The synthesis and properties of peptidylmethylsulphonium salts with two cationic residues as potential inhibitors of prohormone processing.

A Zumbrunn 1, S Stone 1, E Shaw 1
PMCID: PMC1135513  PMID: 3223967

Abstract

Peptidylmethylsulphonium salts incorporating consecutive basic residues at the C-terminus of the peptidyl portion such as -Arg-Arg-, -Arg-Lys-, -Lys-Lys- and -Lys-Arg- were synthesized and examined as proteinase inhibitors. Serine proteinases with a specificity directed towards hydrolysis at cationic residues were found to be unaffected by these derivatives. On the other hand, cysteine proteinases, cathepsin B and, in particular, clostripain were readily inactivated by affinity labelling. The reagents thus are of promise for the study of prohormone processing promoted by cysteine proteinases.

Full text

PDF
989

Selected References

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

  1. Achstetter T., Wolf D. H. Hormone processing and membrane-bound proteinases in yeast. EMBO J. 1985 Jan;4(1):173–177. doi: 10.1002/j.1460-2075.1985.tb02333.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews P. C., Brayton K., Dixon J. E. Precursors to regulatory peptides: their proteolytic processing. Experientia. 1987 Jul 15;43(7):784–790. doi: 10.1007/BF01945356. [DOI] [PubMed] [Google Scholar]
  3. Barrett A. J., Kirschke H. Cathepsin B, Cathepsin H, and cathepsin L. Methods Enzymol. 1981;80(Pt 100):535–561. doi: 10.1016/s0076-6879(81)80043-2. [DOI] [PubMed] [Google Scholar]
  4. Bothwell M. A., Wilson W. H., Shooter E. M. The relationship between glandular kallikrein and growth factor-processing proteases of mouse submaxillary gland. J Biol Chem. 1979 Aug 10;254(15):7287–7294. [PubMed] [Google Scholar]
  5. Davidson H. W., Peshavaria M., Hutton J. C. Proteolytic conversion of proinsulin into insulin. Identification of a Ca2+-dependent acidic endopeptidase in isolated insulin-secretory granules. Biochem J. 1987 Sep 1;246(2):279–286. doi: 10.1042/bj2460279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Docherty K., Carroll R., Steiner D. F. Identification of a 31,500 molecular weight islet cell protease as cathepsin B. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3245–3249. doi: 10.1073/pnas.80.11.3245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Docherty K., Hutton J. C., Steiner D. F. Cathepsin B-related proteases in the insulin secretory granule. J Biol Chem. 1984 May 25;259(10):6041–6044. [PubMed] [Google Scholar]
  8. Evans B., Shaw E. Inactivation of cathepsin B by active site-directed disulfide exchange. Application in covalent affinity chromatography. J Biol Chem. 1983 Sep 10;258(17):10227–10232. [PubMed] [Google Scholar]
  9. Fletcher D. J., Quigley J. P., Bauer G. E., Noe B. D. Characterization of proinsulin- and proglucagon-converting activities in isolated islet secretory granules. J Cell Biol. 1981 Aug;90(2):312–322. doi: 10.1083/jcb.90.2.312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gilles A. M., De Wolf A., Keil B. Amino-acid sequences of the active-site sulfhydryl peptide and other thiol peptides from the cysteine proteinase alpha-clostripain. Eur J Biochem. 1983 Feb 15;130(3):473–479. doi: 10.1111/j.1432-1033.1983.tb07174.x. [DOI] [PubMed] [Google Scholar]
  11. Green G. D., Shaw E. Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases. J Biol Chem. 1981 Feb 25;256(4):1923–1928. [PubMed] [Google Scholar]
  12. Julius D., Brake A., Blair L., Kunisawa R., Thorner J. Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-alpha-factor. Cell. 1984 Jul;37(3):1075–1089. doi: 10.1016/0092-8674(84)90442-2. [DOI] [PubMed] [Google Scholar]
  13. Kettner C., Shaw E. Inactivation of trypsin-like enzymes with peptides of arginine chloromethyl ketone. Methods Enzymol. 1981;80(Pt 100):826–842. doi: 10.1016/s0076-6879(81)80065-1. [DOI] [PubMed] [Google Scholar]
  14. Kettner C., Shaw E. Synthesis of peptides of arginine chloromethyl ketone. Selective inactivation of human plasma kallikrein. Biochemistry. 1978 Oct 31;17(22):4778–4784. doi: 10.1021/bi00615a027. [DOI] [PubMed] [Google Scholar]
  15. Loh Y. P., Brownstein M. J., Gainer H. Proteolysis in neuropeptide processing and other neural functions. Annu Rev Neurosci. 1984;7:189–222. doi: 10.1146/annurev.ne.07.030184.001201. [DOI] [PubMed] [Google Scholar]
  16. Mason A. J., Evans B. A., Cox D. R., Shine J., Richards R. I. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature. 1983 May 26;303(5915):300–307. doi: 10.1038/303300a0. [DOI] [PubMed] [Google Scholar]
  17. Porter W. H., Cunningham L. W., Mitchell W. M. Studies on the active site of clostripain. The specific inactivation by the chloromethyl ketone derived from -N-tosyl-L-lysine. J Biol Chem. 1971 Dec 25;246(24):7675–7682. [PubMed] [Google Scholar]
  18. Prado E. S., Araújo-Viel M. S., Juliano M. A., Juliano L., Stella R. C., Sampaio C. A. Tetrapeptide substrates for the discrimination among kallikreins and other trypsin-like serine proteinases. Biol Chem Hoppe Seyler. 1986 Mar;367(3):199–205. doi: 10.1515/bchm3.1986.367.1.199. [DOI] [PubMed] [Google Scholar]
  19. Rauber P., Walker B., Stone S., Shaw E. Synthesis of lysine-containing sulphonium salts and their properties as proteinase inhibitors. Biochem J. 1988 Mar 15;250(3):871–876. doi: 10.1042/bj2500871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Richards R. I., Catanzaro D. F., Mason A. J., Morris B. J., Baxter J. D., Shine J. Mouse glandular kallikrein genes. Nucleotide sequence of cloned cDNA coding for a member of the kallikrein arginyl esteropeptidase group of serine proteases. J Biol Chem. 1982 Mar 25;257(6):2758–2761. [PubMed] [Google Scholar]
  21. SCHOELLMANN G., SHAW E. A new method for labelling the active center of chymotrypsin. Biochem Biophys Res Commun. 1962 Feb 20;7:36–40. doi: 10.1016/0006-291x(62)90140-7. [DOI] [PubMed] [Google Scholar]
  22. Shaw E. Peptidyl sulfonium salts. A new class of protease inhibitors. J Biol Chem. 1988 Feb 25;263(6):2768–2772. [PubMed] [Google Scholar]
  23. Stone S. R., Hofsteenge J. Specificity of activated human protein C. Biochem J. 1985 Sep 1;230(2):497–502. doi: 10.1042/bj2300497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Virji M. A., Vassalli J. D., Estensen R. D., Reich E. Plasminogen activator of islets of Langerhans: modulation by glucose and correlation with insulin production. Proc Natl Acad Sci U S A. 1980 Feb;77(2):875–879. doi: 10.1073/pnas.77.2.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whitaker J. R., Perez-Villase ñor J. Chemical modification of papain. I. Reaction with the chloromethyl ketones of phenylalanine and lysine and with phenylmethyl-sulfonyl fluoride. Arch Biochem Biophys. 1968 Mar 20;124(1):70–78. doi: 10.1016/0003-9861(68)90304-4. [DOI] [PubMed] [Google Scholar]
  26. Yoi O. O., Seldin D. C., Spragg J., Pinkus G. S., Austen K. F. Sequential cleavage of proinsulin by human pancreatic kallikrein and a human pancreatic kininase. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3612–3616. doi: 10.1073/pnas.76.8.3612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zumbrunn A., Stone S., Shaw E. Synthesis and properties of Cbz-Phe-Arg-CHN2 (benzyloxycarbonylphenylalanylarginyldiazomethane) as a proteinase inhibitor. Biochem J. 1988 Mar 1;250(2):621–623. doi: 10.1042/bj2500621. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES