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Chemical Compound Review

Tosyllysyl chloromethane     N-(7-amino-1-chloro-2-oxo- heptan-3-yl)-4...

Synonyms: Tosyl-K-CMK, Tosyl-Lys-CMK, CHEMBL2316089, CK004, AR-1L2536, ...
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Disease relevance of Chlorotosylamidoaminoheptanone

  • Organophosphorous agents (DFP and PMSF), chloromethyl-ketone derivatives of tosylamino acids (TLCK and TPCK), Actinomyces products (pepstatin and chymostatin), and the synthetic protease substrate TAME inhibited monocyte-mediated cytotoxicity against ActD-treated WEHI 164 cells [1].
  • The protease inhibitor TLCK alters the apparent molecular weights of some measles virus proteins by a mechanism unrelated to inhibition of proteolytic cleavage [2].

High impact information on Chlorotosylamidoaminoheptanone

  • These appeared to be effected by the serine protease activity of factor Xa, since in the presence of serine protease inhibitors such as PMSF, leupeptin, benzamidine, TAP anticoagulant, and TLCK, the latter three being specific inhibitors of the factor Xa, active site, the effects were completely blocked [3].
  • Degradation of H2 in the ER by this alternative pathway is inhibited by TLCK or TPCK, but neither formation nor degradation of the 35-kD fragment is blocked by these reagents [4].
  • Nonlysosomal, pre-Golgi degradation of unassembled asialoglycoprotein receptor subunits: a TLCK- and TPCK-sensitive cleavage within the ER [5].
  • Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies [6].
  • Interestingly, SAM and DCI also prevented cation-induced low MW DNA fragmentation in GC nuclei; however, TLCK and TPCK were without effect [7].

Biological context of Chlorotosylamidoaminoheptanone


Anatomical context of Chlorotosylamidoaminoheptanone


Associations of Chlorotosylamidoaminoheptanone with other chemical compounds

  • The PMA-induced protease, cd43' ase, is characterized by insensitivity to DFP, TLCK, leupeptin, pepstatin, and 1,10 phenanthroline (< 5 mM) [17].
  • The stoichiometry of addition of DFP to the enzyme was 1:1 and only 1 TLCK molecule was found in TLCK-modified enzyme, as measured by mass spectrometry [18].
  • In this study, macronuclear, soluble chromatin was subfractionated using isokinetic sucrose density gradient ultracentrifugation in a buffer consisting of 50 mM NaCl, 1 mM Na2 EDTA, 1 mM TEA HCl, pH 7.0, 0.1 mM TLCK and 0.1 mM PMSF [19].
  • At a functional level, we found that apoptosis was blocked by the protease inhibitor TLCK in CHX-treated but not in serum-deprived cells [20].
  • Furthermore, whereas apoptosis (DNA degradation) triggered by CAM was prevented by the serine protease inhibitor N-tosyl-L-lysylchloromethyl ketone (TLCK), this process was actually potentiated by this inhibitor when induced by CHX [21].

Gene context of Chlorotosylamidoaminoheptanone

  • In addition, TPA up-regulated Smad7 expression in the presence of NF-kappaB inhibitor TLCK [22].
  • The NFkappaB inhibitor (TLCK and PTD-p65), or a specific CaMKII inhibitor (m-AIP), was used to study association of NFkappaB or CaMKII with BDNF expression/secretion in RGC-5 cells [23].
  • TPCK and TLCK each inhibited MnSOD gene expression and NF-kappa B activation [24].
  • When the purification of this diaphorase was carried out in the presence of only three protease inhibitors, PMSF, DIFP and TLCK, a partially proteolyzed form of the diaphorase with a molecular mass of 68 kDa was prepared [25].
  • Inhibition of NF-kappaB activity by overexpression of an IkappaB alpha transdominant inhibitor or exposure to the protease inhibitor TLCK did not inhibit the OA mediated increase in GLCLC transcripts [26].

Analytical, diagnostic and therapeutic context of Chlorotosylamidoaminoheptanone

  • Prolongation of allograft survival in rat heterotopic heart transplantation by TLCK, a serine protease inhibitor [27].
  • They were purified by affinity chromatography on Cystatin-Sepharose, recognized by the polyclonal anti-cruzipain serum, and their activity in gelatin-containing gels was completely abolished by E-64, TLCK, leupeptin, and aprotinin but not by PMSF, pepstatin A, EDTA or 1,10-phenantroline [28].
  • We have confirmed the work of others which showed that the synthetic anti-proteases epilson-aminocaproic acid and tosyl-L-lysyl-chloromethane (TLCK) also inhibited mitogen-induced blastogenesis and we have shown that phenylmethylsulfonylfluride was effective also; all of these agents were found to inhibit the MLR as well [29].


  1. Rapid killing of actinomycin D-treated tumor cells by human monocytes. II. Cytotoxicity is independent of secretion of reactive oxygen intermediates and is suppressed by protease inhibitors. Colotta, F., Bersani, L., Lazzarin, A., Poli, G., Mantovani, A. J. Immunol. (1985) [Pubmed]
  2. The protease inhibitor TLCK alters the apparent molecular weights of some measles virus proteins by a mechanism unrelated to inhibition of proteolytic cleavage. Wechsler, S.L., Weyand, S., Goosmann, A., Burge, B.W. Virology (1982) [Pubmed]
  3. Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat. Ko, F.N., Yang, Y.C., Huang, S.C., Ou, J.T. J. Clin. Invest. (1996) [Pubmed]
  4. Two pathways for the degradation of the H2 subunit of the asialoglycoprotein receptor in the endoplasmic reticulum. Yuk, M.H., Lodish, H.F. J. Cell Biol. (1993) [Pubmed]
  5. Nonlysosomal, pre-Golgi degradation of unassembled asialoglycoprotein receptor subunits: a TLCK- and TPCK-sensitive cleavage within the ER. Wikström, L., Lodish, H.F. J. Cell Biol. (1991) [Pubmed]
  6. Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Lazebnik, Y.A., Takahashi, A., Moir, R.D., Goldman, R.D., Poirier, G.G., Kaufmann, S.H., Earnshaw, W.C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. High and low molecular weight DNA cleavage in ovarian granulosa cells: characterization and protease modulation in intact cells and in cell-free nuclear autodigestion assays. Trbovich, A.M., Hughes, F.M., Perez, G.I., Kugu, K., Tilly, K.I., Cidlowski, J.A., Tilly, J.L. Cell Death Differ. (1998) [Pubmed]
  8. Decrease of metastatogenic potential by pregraft treatment of Lewis lung carcinoma cells with proteinase and protein kinase affinity labels. Stahl, K.W., Mathé, G., Kovacs, G. Cancer Res. (1985) [Pubmed]
  9. Effects of putative protease inhibitors on the acrosome reaction of sea urchin spermatozoa. Hyne, R.V., Garbers, D.L. J. Reprod. Fertil. (1982) [Pubmed]
  10. Laser-beam-triggered microcavitation: a novel method for selective cell destruction. Leszczynski, D., Pitsillides, C.M., Pastila, R.K., Rox Anderson, R., Lin, C.P. Radiat. Res. (2001) [Pubmed]
  11. Putative rat sperm lipid-binding protein: isolation and partial characterization. Pryor, J.L., Xu, W., Moore, A., Ensrud, K.M., Hamilton, D.W. Mol. Reprod. Dev. (1994) [Pubmed]
  12. Complement factor D-like activity of Porphyromonas gingivalis W83. Schenkein, H.A. Oral Microbiol. Immunol. (1991) [Pubmed]
  13. A chymotryptic-type protease inhibitor decreases interleukin 2 synthesis and induces prostaglandin production in Jurkat T cells. Auberger, P., Didier, M., Didier, J., Aussel, C., Fehlmann, M. Cell. Signal. (1989) [Pubmed]
  14. Inhibition or killing of an intracellular pathogen by activated macrophages is abrogated by TLCK or aminophylline. McLeod, R., Remington, J.S. Immunology (1980) [Pubmed]
  15. Evidence that protease action is not specifically involved in the hatching of rabbit blastocysts caused by commercial bovine serum albumin in culture. Kane, M.T. J. Reprod. Fertil. (1983) [Pubmed]
  16. Human lymphokine-activated killer (LAK) cells: III. Effect of L-phenylalanine methyl ester on LAK cell activation from human peripheral blood mononuclear cells: possible protease involvement of monocytes, natural killer cells and LAK cells. Leung, K.H. Cancer Immunol. Immunother. (1991) [Pubmed]
  17. Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils. Remold-O'Donnell, E., Parent, D. J. Immunol. (1994) [Pubmed]
  18. Purification and characterization of PrbA, a new esterase from Enterobacter cloacae hydrolyzing the esters of 4-hydroxybenzoic acid (parabens). Valkova, N., Lépine, F., Labrie, L., Dupont, M., Beaudet, R. J. Biol. Chem. (2003) [Pubmed]
  19. Subfractionation of soluble macronuclear chromatin and enrichment of specific genes as chromatin from Euplotes eurystomus. Cadilla, C.L., Roberson, A.E., Harp, J., Olins, A.L., Olins, D.E. Nucleic Acids Res. (1986) [Pubmed]
  20. Serum deprivation and protein synthesis inhibition induce two different apoptotic processes in N18 neuroblastoma cells. Boix, J., Fibla, J., Yuste, V., Piulats, J.M., Llecha, N., Comella, J.X. Exp. Cell Res. (1998) [Pubmed]
  21. Different patterns of apoptosis of HL-60 cells induced by cycloheximide and camptothecin. Gong, J., Li, X., Darzynkiewicz, Z. J. Cell. Physiol. (1993) [Pubmed]
  22. Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells. Tsunobuchi, H., Ishisaki, A., Imamura, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  23. The role of CaMKII in BDNF-mediated neuroprotection of retinal ganglion cells (RGC-5). Fan, W., Agarwal, N., Cooper, N.G. Brain Res. (2006) [Pubmed]
  24. Thiol modulation of TNF alpha and IL-1 induced MnSOD gene expression and activation of NF-kappa B. Das, K.C., Lewis-Molock, Y., White, C.W. Mol. Cell. Biochem. (1995) [Pubmed]
  25. Purification of an NADPH-dependent diaphorase from membrane of DMSO-induced differentiated human promyelocytic leukemia HL-60 cells. Otsuka-Murakami, H., Nisimoto, Y. FEBS Lett. (1995) [Pubmed]
  26. Expression of glutathione and gamma-glutamylcysteine synthetase mRNA is Jun dependent. Sekhar, K.R., Meredith, M.J., Kerr, L.D., Soltaninassab, S.R., Spitz, D.R., Xu, Z.Q., Freeman, M.L. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  27. Prolongation of allograft survival in rat heterotopic heart transplantation by TLCK, a serine protease inhibitor. Morrissey, P.E., Gollin, G., Brusett, K., Marks, W.H. Transplantation (1994) [Pubmed]
  28. Trypanosoma cruzi: partial characterization of minor cruzipain isoforms non-adsorbed to Concanavalin A-Sepharose. Duschak, V.G., Barboza, M., Couto, A.S. Exp. Parasitol. (2003) [Pubmed]
  29. Inhibition of lymphocyte transformation: effect of soy bean trypsin inhibitor and synthetic anti-proteases. Moreau, P., Dornand, J., Kaplan, J.G. Can. J. Biochem. (1975) [Pubmed]
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