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. 1988 Dec 1;256(2):481–486. doi: 10.1042/bj2560481

Synthesis and properties of peptidyl derivatives of arginylfluoromethanes.

H Angliker 1, P Wikström 1, P Rauber 1, S Stone 1, E Shaw 1
PMCID: PMC1135435  PMID: 3223925

Abstract

Two peptide derivatives of arginylfluoromethane (Arg-CH2F), namely Bz(benzoyl)-Phe-ArgCH2F and D-Phe-Pro-Arg-CH2F, have been synthesized by extension of available methods, i.e. the Dakin-West reaction [Rasnick (1985) Anal. Biochem. 149, 461-465] or synthesis of a phthaloyl-blocked C-terminal fluoromethane [Rauber, Angliker, Walker & Shaw (1986) Biochem. J. 239, 633-640; Angliker, Wikström, Rauber & Shaw (1987) Biochem. J. 241, 871-875] with subsequent elongation. The guanidino group of arginine was protected as the bis-Cbz (benzyloxycarbonyl) derivative. The products were examined as active-site-directed inhibitors of some trypsin-related serine proteinases as well as a pair of cysteine proteinases. The results extend previous observations that the rate of alkylation of serine proteinases by fluoromethanes may be considerably slower than by chloromethanes. As expected, the amino acid sequence of the inhibitors influenced their relative effectiveness. Thus the rate of inactivation of a number of trypsin-like proteinases by D-Phe-Pro-Arg-CH2F varied by more than two orders of magnitude.

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Selected References

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

  1. Angliker H., Wikstrom P., Rauber P., Shaw E. The synthesis of lysylfluoromethanes and their properties as inhibitors of trypsin, plasmin and cathepsin B. Biochem J. 1987 Feb 1;241(3):871–875. doi: 10.1042/bj2410871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Collen D., Matsuo O., Stassen J. M., Kettner C., Shaw E. In vivo studies of a synthetic inhibitor of thrombin. J Lab Clin Med. 1982 Jan;99(1):76–83. [PubMed] [Google Scholar]
  4. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Fiedler F., Hirschauer C., Fritz H. Inhibition of three porcine glandular kallikreins by chloromethyl ketones. Hoppe Seylers Z Physiol Chem. 1977 Apr;358(4):447–451. doi: 10.1515/bchm2.1977.358.1.447. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Green G. D., Shaw E. Thiobenzyl benzyloxycarbonyl-L-lysinate, substrate for a sensitive colorimetric assay for trypsin-like enzymes. Anal Biochem. 1979 Mar;93(2):223–226. doi: 10.1016/s0003-2697(79)80141-4. [DOI] [PubMed] [Google Scholar]
  9. Hofsteenge J., Taguchi H., Stone S. R. Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. Biochem J. 1986 Jul 1;237(1):243–251. doi: 10.1042/bj2370243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imperiali B., Abeles R. H. Extended binding inhibitors of chymotrypsin that interact with leaving group subsites S1'-S3'. Biochemistry. 1987 Jul 14;26(14):4474–4477. doi: 10.1021/bi00388a044. [DOI] [PubMed] [Google Scholar]
  11. Imperiali B., Abeles R. H. Inhibition of serine proteases by peptidyl fluoromethyl ketones. Biochemistry. 1986 Jul 1;25(13):3760–3767. doi: 10.1021/bi00361a005. [DOI] [PubMed] [Google Scholar]
  12. JEPSON J. B., SMITH I. Multiple dipping procedures in paper chromatography: a specific test for hydroxy-proline. Nature. 1953 Dec 12;172(4389):1100–1101. doi: 10.1038/1721100b0. [DOI] [PubMed] [Google Scholar]
  13. KITZ R., WILSON I. B. Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem. 1962 Oct;237:3245–3249. [PubMed] [Google Scholar]
  14. Kettner C., Mirabelli C., Pierce J. V., Shaw E. Active site mapping of human and rat urinary kallikreins by peptidyl chloromethyl ketones. Arch Biochem Biophys. 1980 Jul;202(2):420–430. doi: 10.1016/0003-9861(80)90446-4. [DOI] [PubMed] [Google Scholar]
  15. Kettner C., Shaw E. D-Phe-Pro-ArgCH2C1-A selective affinity label for thrombin. Thromb Res. 1979;14(6):969–973. doi: 10.1016/0049-3848(79)90014-8. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Lottenberg R., Jackson C. M. Solution composition dependent variation in extinction coefficients for p-nitroaniline. Biochim Biophys Acta. 1983 Feb 15;742(3):558–564. doi: 10.1016/0167-4838(83)90273-x. [DOI] [PubMed] [Google Scholar]
  19. Rasnick D. Synthesis of peptide fluoromethyl ketones and the inhibition of human cathepsin B. Anal Biochem. 1985 Sep;149(2):461–465. doi: 10.1016/0003-2697(85)90598-6. [DOI] [PubMed] [Google Scholar]
  20. Rauber P., Angliker H., Walker B., Shaw E. The synthesis of peptidylfluoromethanes and their properties as inhibitors of serine proteinases and cysteine proteinases. Biochem J. 1986 Nov 1;239(3):633–640. doi: 10.1042/bj2390633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shaw E., Glover G. Further observations on substrate-derived chloromethyl ketones that inactivate trypsin. Arch Biochem Biophys. 1970 Aug;139(2):298–305. doi: 10.1016/0003-9861(70)90481-9. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Walker B., Wikstrom P., Shaw E. Evaluation of inhibitor constants and alkylation rates for a series of thrombin affinity labels. Biochem J. 1985 Sep 15;230(3):645–650. doi: 10.1042/bj2300645. [DOI] [PMC free article] [PubMed] [Google Scholar]

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