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

• These compounds demonstrate divergent protease specificity and, in the case of TLCK and TPCK, convergent reactivity toward the highly conserved protein kinase catalytic subunit [8].
• When incubation with inhibitors was extended to 2 h only TLCK and its hydrolysis products inhibited the jelly-induced acrosome reaction [9].
• Intracytoplasmic release of lysosomal hydrolases is, in part, responsible for cell death, because the protease inhibitors E64d and TLCK diminished cell killing [10].
• To obtain internal amino acid sequences, the isolated protein was cleaved either with cyanogen bromide in 70% formic acid or with TLCK-treated chymotrypsin [11].
• Furthermore, during complement activation, only a small number of C3 molecules accumulate on the surface of this organism unless the bacteria are treated with the protease inhibitor TLCK prior to complement activation [12].

Anatomical context of Chlorotosylamidoaminoheptanone

• Prostaglandin synthesis, a process that is known to reduce IL2 production in T cells, was increased by TPCK but not by TLCK, suggesting that this process could be, at least in part, responsible for the inhibition of IL2 production [13].
• Tosyllysine chloromethyl ketone (TLCK) and aminophylline abrogate inhibition or killing of Toxoplasma gondii by activated macrophages [14].
• Ovomucoid trypsin inhibitor, TAME and TLCK significantly inhibited blastocyst hatching but only at the highest concentration used [15].
• TLCK did not prevent depletion of monocytes nor inhibition of NK activity induced by PheOMe [16].
• TPCK but not TLCK inhibited rIL-2 induction of LAK cells [16].

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].

References