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 (Ki = 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
Inhibitor of serine proteinases having a chymotrypsin-like specificity like α-, β-, δ- and γ-chymotrypsin, chymases, cathepsin G, and most cysteine proteinases including papain and cathepsin A, B, H, and L. Mixture of type A (R=L-Leu), type B (R=L-Val), type C (R=L-Ile).
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:
① 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
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) Umezawa?et al.?(1970),?Chymostatin, a new chymotrypsin inhibitor produced by actinomycetes; J. Antibiot. (Tokyo)?23?425
2) Johnson?et al.?(1998),?Inactivation of chymotrypsin and human skin chymase: kinetics of time-dependent inhibition in the presence of substrate; Biochim. Biophys. Acta?953?269
3) Stein and Strimpler (1987),?Slow-binding of chymotrypsin and cathepsin G by the peptide aldehyde chymostatin; Biochemistry?26?2611
4) Roszkowska-Chojecka?et al.?(2015),?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; Exp. Physiol.?100?1093
