Figueiredo-Pereira M E, Banik N, Wilk S
Department of Pharmacology, Mount Sinai School of Medicine, CUNY, New York 10029.
J Neurochem. 1994 May;62(5):1989-94. doi: 10.1046/j.1471-4159.1994.62051989.x.
The potencies of three peptide aldehyde inhibitors of calpain (calpain inhibitors 1 and 2 and calpeptin) as inhibitors of four catalytic activities of the multicatalytic proteinase complex (MPC) were compared with their potencies as inhibitors of m-calpain. The chymotrypsinlike activity (cleavage after hydrophobic amino acids) and the caseinolytic activity (degradation of beta-casein) of MPC were strongly inhibited by calpain inhibitors 1 and 2 (IC50 values in the low micromolar range). Cleavage by MPC after acidic amino acids (peptidylglutamyl-peptide bond hydrolyzing activity) and basic amino acids (trypsinlike activity) was inhibited less effectively, declining moderately with increasing concentrations of calpain inhibitors 1 and 2. Calpeptin only weakly inhibited the four MPC activities, yet was the most potent inhibitor of m-calpain. These results indicate that caution must be exercised when calpain inhibitors 1 and 2 are used to infer calpain function. Calpeptin may be a better choice for such studies, although its effect on other cysteine or serine proteinases remains to be determined.
比较了三种钙蛋白酶肽醛抑制剂（钙蛋白酶抑制剂1和2以及抑肽素）作为多催化蛋白酶复合物（MPC）四种催化活性抑制剂的效力与其作为m-钙蛋白酶抑制剂的效力。钙蛋白酶抑制剂1和2强烈抑制MPC的类胰凝乳蛋白酶活性（在疏水氨基酸后切割）和酪蛋白分解活性（β-酪蛋白降解）（IC50值在低微摩尔范围内）。MPC在酸性氨基酸后切割（肽基谷氨酰肽键水解活性）和碱性氨基酸后切割（类胰蛋白酶活性）受到的抑制效果较差，随着钙蛋白酶抑制剂1和2浓度的增加适度下降。抑肽素仅微弱抑制MPC的四种活性，但却是m-钙蛋白酶最有效的抑制剂。这些结果表明，当使用钙蛋白酶抑制剂1和2来推断钙蛋白酶功能时必须谨慎。对于此类研究，抑肽素可能是更好的选择，尽管其对其他半胱氨酸或丝氨酸蛋白酶的影响仍有待确定。
