CHYMOSTATIN Chemical Properties

Melting point:

205 °C

storage temp. 

-20°C

solubility 

DMSO: 10 mM Stock solutions stable for months at −20 °C.

form 

White to slightly yellow solid or powder

color 

White or off-white

biological source

microbial

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

InChIKey

MRXDGVXSWIXTQL-HYHFHBMOSA-N

SMILES

OC(C(NC(NC(C1NC(NCC1)=N)C([F,Cl,Br,I]C)=O)=O)CC2=CC=CC=C2)=O

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

22-24/25-36-26

WGK Germany 

3

RTECS 

GC3047700

F 

10-21

Storage Class

11 - Combustible Solids

MSDS

• Language:English Provider:SigmaAldrich

CHYMOSTATIN Usage And Synthesis

Description

Chymostatin is a bioactive peptide of microbial origin that acts as a protease inhibitor with selectivity for chymotryptase-like serine proteases. It potently inhibits chymotrypsin and chymase (K_i = 9.36 and 13.1 nM, respectively) while less effectively blocking the activity of cathepsins, papain, and leukocyte elastase. It is without effect on trypsin, thrombin, plasmin, pepsin, and kallikrein.

Uses

Chymostatin has been used in a study that determined that molecular calculations are useful for evaluating the interactions between ligands, including inhibitors and homologous enzymes, in docking models. Chymostatin has also been used in a study to investigate the norovirus protease as an attractive target for antiviral drug development.

Uses

Chymostatin is a specific inhibitor of α-, β-, γ-, and δ-chymotrypsin.

General Description

Chymostatin is a mixture of three components, A, B, and C. The component A being N-[((S)-1-carboxy-2-phenylethyl)-carbamoyl]-α-[2-iminohexahydro-4(S)-pyrimidyl]-L-glycyl-L-leucyl-phenylalaninal. The other two components B and C differ in that the L-leucyl residue is substituted by L-valine and L-isoleucine, respectively.

Biochem/physiol Actions

Chymostatin is a strong inhibitor of many proteases, including chymotrypsin, papain, chymotrypsin-like serine proteinases, chymases, and lysosomal cysteine proteinases such as cathepsins A,B,C, B, H, and L. It weakly inhibits human leucocyte elastase. It is effective at a final concentration of 100 to 200 μg/ml (10 to 100 μM). Chymostatin is often included in protease inhibitor cocktails used with plant extracts.

Synthesis

The preparation of potato pancreatic coagulation protease inhibitor included the following steps: ?? Extraction: fresh potatoes were washed and chopped and soaked in 7 g/L sodium disulfite hydrosulfite solution for 30 min. Go to the supernatant, and then add the number of tubes into 50 ml of the same solution, placed in the tissue masher stirred to homogenization. Filter, adjust filtrate to pH 3.0, centrifuge, and collect centrifugate. (ii) Salt folding: at 5?? C., add solid sulphuric acid money to the centrifugal solution to 70% saturation, stir for l hour, centrifuge, suspend the precipitate in a sulphuric acid press of the same saturation, filter through whatmaln No. filter paper at room temperature and wash. The precipitate is dissolved in distilled water now stirred, filtered, and the filtrate retained. (iii) Heat treatment: the filtrate is placed in a 70?? C. water bath for 5 minutes, filtered, and the filtrate is kept for dialysis. ?? dialysis: filtrate into the permeable folding bag, placed in the refrigerator on the distilled water permeable folding 48 hours, during the replacement of several times the distilled water. Filter, filtrate freeze-dried into powder. ?? Separation: Sephadex is used to separate the powder. ?? Separation: SephadexG-75 gel was heat solubilized with 0.05M, pHs.ZTris-HCI starting buffer (containing 0.1MKCI) for a month, and loaded on a column (20x50 cm) after depressurization to remove air bubbles. Equilibrate. 20 mg of cold lyophilized powder was dissolved in 5 ml of buffer, centrifuged, and loaded onto the column. Elute with starting buffer at a flow rate of 60 ml/hr and collect 5 ml in sections. The light absorption values of the collected solution in each tube at 280 cm were measured to obtain the elution graph. Peak I and peak l were collected separately and freeze-dried.

in vitro

chymostatin was found to be a potent inhibitor of human leucocyte chymotrypsin-like protease. its affinity to the leucocyte protease was found to be much higher than its affinity to bovine pancreatic alpha-chymotrypsin. chymsotatin also showed a weak inhibitory effect on the activity of human leucocyte elastase. in addition, the preincubation of chymostatin with 35so2-4-labeled cartilage before the addition of the human chymotrypsin-like protease to the tissue could also inhibit 35so2-4 release [1].

in vivo

the effect of chymostatin on c57bl/6j-dy dystrophic mice was studied. the locomotor activity of normal mice markedly increased, attaining a plateau at 8 weeks of age. serum levels of creatine phosphokinase were much higher in dystrophic mice when compared with normal mice, and dystrophic mice also showed a reduced muscle protein content. when 3-week-old dystrophic mice received chymostatin at 1 mg/kg, the decrease in locomotor activity could be retarded, serum enzyme levels significantly decreased, and muscle protein content also obviously increased. in addition, the survival time of chymostatin-treated dystrophic mice was prolonged [2].

References

[1] H UMEZAWA. Chymostatin, a new chymotrypsin inhibitor produced by actinomycetes.[J]. Journal of Antibiotics, 1970, 23 8: 425-427. DOI:10.7164/antibiotics.23.425
[2] LAMBRO A. JOHNSON  Mark E  Kenneth E Moon. Inactivation of chymotrypsin and human skin chymase: Kinetics of time-dependent inhibition in the presence of substrate[J]. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1988, 953: Pages 269-279. DOI:10.1016/0167-4838(88)90035-0
[3] ROSS L. STEIN  Anne M S. Slow-binding inhibition of chymotrypsin and cathepsin G by the peptide aldehyde chymostatin[J]. Biochemistry Biochemistry, 1987, 26 9: 2611-2615. DOI:10.1021/bi00383a030
[4] MALWINA MONIKA ROSZKOWSKA-CHOJECKA. Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensin II, renal haemodynamics and renal excretion in two models of hypertension in the rat[J]. Experimental Physiology, 2015, 100 9: 1093-1105. DOI:10.1113/ep085325

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