4272-74-6

Basic information

• Product Name: TLCK
• Synonyms: Chloro-3-tosylaMido-7-aMino-2-heptanone-HCl research grade;(S)-N-(7-AMino-1-chloro-2-oxoheptan-3-yl)-4-MethylbenzenesulfonaMide hydrochloride;Benzenesulfonamide,N-[(1S)-5-amino-1-(2-chloroacetyl)pentyl]-4-methyl-, hydrochloride (1:1);Tosyl-L-lysyl-chloromethane hydrochloride;Nα-Tosyl-L-lysine chloromethylketone hydrochloride≥ 98% (HPLC);Tos-L-Lys-CMK·HCl;L-1-CHLORO-3-TOSYLAMIDO-7-AMINO-2-HEPTANONE HCL;L-1-CHLORO-3-(4-TOSYLAMIDO)-7-AMINO-2-HEPTANONE HYDROCHLORIDE
• CAS NO: 4272-74-6
• Molecular Formula: C14H22Cl2N2O3S
• Molecular Weight: 369.31
• EINECS: 224-266-4
• Product Categories: inhibitor
• Mol File: 4272-74-6.mol
• Article Data: 0

Chemical Properties

• Melting Point: ~165 °C (dec.)
• Boiling Point: 509.8 °C at 760 mmHg
• Flash Point: 262.1 °C
• Appearance: white to pink/powder
• Density: g/cm³
• Vapor Pressure: 1.65E-10mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: H2O: 50 mg/mL
• BRN: 7106867
• CAS DataBase Reference: TLCK(CAS DataBase Reference)
• NIST Chemistry Reference: TLCK(4272-74-6)
• EPA Substance Registry System: TLCK(4272-74-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: UN 3335
• WGK Germany: 3
• RTECS: XT5160000
• F: 10-21
• Hazardous Substances Data: 4272-74-6(Hazardous Substances Data)

Usage

Chemical Properties

white to light beige powder

Uses

Different sources of media describe the Uses of 4272-74-6 differently. You can refer to the following data:
1. Tosyllysine chloromethylketone (TLCK) is an active site-directed agent that inhibits serine proteinases with trypsin-like activity. TLCK may also act non-selectively with thiol groups and thereby inhibit cysteine proteinases and other enzymes. To prevent proteolytic degradation, TLCK may be used in protein purification protocols. TLCK selectively inactiviates clostripain obtained from C. histolyticum.
2. Nα-Tosyl-L-lysine chloromethyl ketone hydrochloride has been used:in chymotrypsin purification to prevent binding of trypsins to the affinity support by inhibiting them in the crude extractas a protease inhibitor in tissue and cell homogenizationas a trypsin inhibitor to determine the specific protease activity levels

Biological Activity

tosyllysine chloromethyl ketone (hydrochloride) is a protease inhibitor [1][2][3].l-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone-hcl (tlck) is a protease inhibitor. tlck is an active site-directed agent that inhibits serine proteinases with trypsin-like activity. tlck also interacts non-selectively with thiol groups and thereby inhibits cysteine proteinases and other enzymes. in lps-activated rat alveolar macrophages, tlck at 1-100 μm inhibited nox- accumulation and inducible inos expression in a concentration-dependent way [1]. to prevent proteolytic degradation, tlck may be used in protein purification protocols [2]. tlck significantly increased the cytotoxic activity of c. histolyticum supernatant towards human epithelial hela cells probably by hindering natural defence mechanisms of cells. 30 min incubation with bacterial supernatant increased toxicity in both concentrations (200 and 1000 μm) from 18 ± 3% to 39 ± 3% and 57 ± 8%, respectively. tlck also blocked clostripain enzymatic activity obtained from c. histolyticum. so tlck might be used to treat diseases complicated by concurrent c. histolyticum infection [3].

Biochem/physiol Actions

Nα-Tosyl-L-lysine chloromethyl ketone hydrochloride (TLCK) blocks the lipopolysaccharide (LPS)- or cytokine-induced activation of nuclear factor κB (NF-κB), which, in turn, blocks the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) transcription. Blocks activation of pp70s6k by all mitogens. Blocks apoptosis in cell lines by inhibiting the processing of caspases in some cell lines and to some stimuli.

Purification Methods

The hydrochloride slowly crystallises from a concentrated solution in absolute EtOH, thinned with EtOH/Et2O for collection and dried in vacuo. It is a suicide enzyme inhibitor of serine proteases, e.g. trypsin and clostripain. [Matsuda et al. Chem Pharm Bull Jpn 30 2512 1982, Shaw et al. Biochemistry 4 2219 1965].

references

[1]. griscavage jm, wilk s, ignarro lj. serine and cysteine proteinase inhibitors prevent nitric oxide production by activated macrophages by interfering with transcription of the inducible no synthase gene. biochem biophys res commun. 1995 oct 13;215(2):721-9.[2]. urban mk, franklin sg, zweidler a. isolation and characterization of the histone variants in chicken erythrocytes. biochemistry. 1979 sep 4;18(18):3952-60.[3]. józwiak, j.,komar, a.,jankowska, e., et al. determination of the cytotoxic effect of clostridiumhistolyticum culture supernatant on hela cells in the presence of protease inhibitors. fems immunology & medical microbiology 45(2):137-42 (2005).

InChI:InChI=1/C14H21ClN2O3S/c1-11-5-7-12(8-6-11)21(19,20)17-13(14(18)10-15)4-2-3-9-16/h5-8,13,17H,2-4,9-10,16H2,1H3/p+1/t13-/m0/s1