|Irriversible cysteine protease inhibitor|
Sample solution is provided at 25 µL, 10mM.
|E-64 is a natural, potent, and irreversible inhibitor of cysteine proteases.Its IC50 values for inhibiting cathepsins K, S, and L, in vitro, are 1.4, 4.1, and 2.5 nM, respectively.|
|Targets||cathepsins K||cathepsins S||cathepsins L|
|Cas No.||66701-25-5||SDF||Download SDF|
|Chemical Name||(2S,3S)-3-[[(2S)-1-[4-(diaminomethylideneamino)butylamino]-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid|
|Solubility||Soluble in water||Storage||Store at 2-8°C|
|Shipping Condition:||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
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Actinidin, a member of C1 family cysteine proteases, has many advantages, including a wide pH activity and wide substrate specificity, which make it a good model system to study enzyme-substrate interations.
E-64, a cysteine protease inhibitor, decreased rates of Giardia trophozoites growth, adherence and viability by > 50% indicating it interferes in some crucial processes involved in parasite survival.
E-64 not only promoted blastocyst development of SCNT embryos but also increased the cryosurvival rates of IVF and SCNT blastocysts. IVF and SCNT blastocysts derived from E-64-treated group were characterized by increased total cell numbers, decreased apoptotic nuclei, suppressed Bax expression and stimulated Bcl-xL expression.
E-64-d, a calpain inhibitor capable of preventing PKC degradation, diminished Aβ-induced decrease of sAPPα secretion.
E-64, a cathepsin inhibitor, has been investigated for its in vitro effect on dental endogenous cathepsins and its most effective molarity to elevate dentin-resin bouding durability.
A new class of compounds that show promise of acting as class-specific inhibitors for the cysteine proteinases are the L-trans-epoxysuccinylpeptides related to the compound E-64 [L-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butanel , isolated from cultures of Aspergillus. E-64 was shown to inhibit papain, ficin and the fruit and stem bromelains, with disappearance of the thiol group of papain1.
E-64 has been reported to inhibit two other mammalian cysteine proteinases: cathepsin L3 and a proteinase from human breast-tumour tissue4 and the calcium-dependent proteinase, calpain, from chicken muscle5. All of these characteristics suggested that E-64 might be a valuable inhibitor for the study of cysteine proteinases.
Lineweaver-Burk plots of inhibition data show that the action of E-64 was not competitive with substrate1 . Moreover, the optical isomerism of the epoxysuccinyl moiety seemed to have no effect on the activity of E-64 as an inhibitor of papain6, 7 .If E-64 were indeed acting by covalent reaction at the active site, its rate of reaction would be decreased by the presence of leupeptin, a tight-binding reversible inhibitor8.
E-64 inhibits only cysteine proteinases. Papain showed a particularly high reactivity with E-64, and good rates were also obtained with the other plant enzymes and the lysosomal cysteine proteinases. There is structural evidence that these enzymes form a homologous group9, and they resemble each other in having Mr about 25 000, no (detected) zymogens and no distinct requirement for calcium. Chicken skeletal-muscle calpain is reported to be inhibited by E-64, but the rate constant has not been determined5.
The most obvious practical application of E-64 is in the active-site titration of the papain-related cysteine proteinases. Active-site titration as a method of determining enzyme concentration has the advantage over rate assays of being insensitive to reaction conditions, and giving a result in active-site molarity10 (Bender et al., 1966).
1. A. J. BARRETT, A. A. KEMBHAVI, L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem. J. (1982) 201, 189-198
2. Hanada, K., Tamai, M., Yamagishi, M., Ohmura, S., Sawada, J. & Tanaka, I. (1978c) Agric. Biol. Chem. 42, 523-528
3. Towatari, T., Tanaka, K., Yoshikawa, D. & Katunuma, N. (1978).J. Biochem. (Tokyo) 84, 659-671.
4. Mort, J. S., Recklies, A. D. & Poole, A. R. (1980) Biochim. Biophys. Acta 614, 134-143.
5. Sugita, H., Ishiura, S., Suzuki, K. & Imahori, K. (1980) J. Biochem. (Tokyo) 87, 339-341
6. Hanada, K., Tamai, M., Morimoto, S., Adachi, T.,Ohmura, S., Sawada, J. & Tanaka, I. (1978a) Agric. Biol. Chem. 42, 537-541.
7. Hanada, K., Tamai, M., Ohmura, S., Sawada, J., Seki, T.& Tanaka, I. (1978b)Agric. Biol. Chem. 42, 529-536
8. Knight, C. G. (1980) Biochem. J. 189,447-453
9. Takio, K., Towatari, T., Katunuma, N. & Titani, K.(1980) Biochem. Biophys. Res. Commun. 97, 340-346
10. Bender, M. L., Begue-Canton, M. L., Blakeley, R. L.,Brubacher, L. J., Feder, J., Gunter, C. R., Kezdy, F. J.,Killheffer, J. V., Marshall, T. H., Miller, C. G., Roeske,R. W. & Stoops, J. K. (1966) J. Am. Chem. Soc. 88,5890-5913