Mehdi S, Angelastro M R, Burkhart J P, Koehl J R, Peet N P, Bey P
Merrell Dow Research Institute, Cincinnati, OH 45215.
Biochem Biophys Res Commun. 1990 Jan 30;166(2):595-600. doi: 10.1016/0006-291x(90)90850-m.
Neutrophil elastase and cathepsin G are serine proteases that can damage connective tissue and trigger other pathological reactions. Compounds containing a peptide sequence to impart specificity and bearing an alpha-dicarbonyl unit (alpha-diketone or alpha-keto ester) at the carboxy terminus are potent inhibitors of the neutrophil serine proteases (human neutrophil elastase: R-Val-COCH3, Ki = 0.017 microM; R-Val-COOCH3, Ki = 0.002 microM; human neutrophil cathepsin G: R-Phe-COCH3, Ki = 0.8 microM; R-Phe-COOCH3, Ki = 0.44 microM; R = N-(4-[(4-chlorophenyl)sulfonylaminocarbonyl]phenylcarbonyl)+ ++ValylProlyl).
中性粒细胞弹性蛋白酶和组织蛋白酶G是能够破坏结缔组织并引发其他病理反应的丝氨酸蛋白酶。含有赋予特异性的肽序列且在羧基末端带有α-二羰基单元（α-二酮或α-酮酯）的化合物是中性粒细胞丝氨酸蛋白酶的有效抑制剂（人中性粒细胞弹性蛋白酶：R-缬氨酸-COCH3，Ki = 0.017微摩尔；R-缬氨酸-COOCH3，Ki = 0.002微摩尔；人中性粒细胞组织蛋白酶G：R-苯丙氨酸-COCH3，Ki = 0.8微摩尔；R-苯丙氨酸-COOCH3，Ki = 0.44微摩尔；R = N-(4-[(4-氯苯基)磺酰氨基羰基]苯基羰基）+缬氨酰脯氨酰）。
