Gray R D, Miller R B, Spatola A F
J Cell Biochem. 1986;32(1):71-7. doi: 10.1002/jcb.240320108.
The following thiol-containing peptide analogues of the carboxyl side of the collagenase-sensitive bond of collagen were synthesized and tested as inhibitors of collagenases partially purified from homogenates of rabbit V-2 tumor and culture medium of pig synovium: HSCH2CH(CH3)CO-Ala-OEt (I), HSCH2CH(CH2Ph)CO-Ala-OEt (II), HSCH2CH[CH2CH(CH3)2]CO-Ala-OEt (III); HSCH2 CH-[CH2CH(CH3)2]CO-Ala-Gly-OEt (IV); HSCH2CH[CH2CH(CH3)2]CO-Ala-Gly-Gln (V). The compounds are listed in order of their inhibitory potency when assayed with nonfibrillar-acid-soluble calf skin collagen at pH 7.6, 35 degrees C. The best inhibitor (III) gave 50% inhibition between 1 and 4 microM. II was a competitive inhibitor with a Ki value of 75 microM. The enzymes preferred an isobutyl side chain at the 2-carbon position, and, where tested (III, IV), did not discriminate strongly between stereoisomers at the chiral 2-carbon. Increasing the length of the inhibitor did not markedly increase potency.
合成了胶原蛋白中胶原酶敏感键羧基侧的以下含硫醇肽类似物，并作为从兔V-2肿瘤匀浆和猪滑膜培养基中部分纯化的胶原酶抑制剂进行了测试：HSCH2CH(CH3)CO-Ala-OEt（I）、HSCH2CH(CH2Ph)CO-Ala-OEt（II）、HSCH2CH[CH2CH(CH3)2]CO-Ala-OEt（III）；HSCH2 CH-[CH2CH(CH3)2]CO-Ala-Gly-OEt（IV）；HSCH2CH[CH2CH(CH3)2]CO-Ala-Gly-Gln（V）。当在pH 7.6、35℃下用非纤维状酸溶性小牛皮胶原蛋白进行测定时，这些化合物按其抑制效力的顺序列出。最佳抑制剂（III）在1至4微摩尔之间产生50%的抑制作用。II是一种竞争性抑制剂，Ki值为75微摩尔。这些酶在2-碳位置优先选择异丁基侧链，并且在测试（III、IV）时，对手性2-碳处的立体异构体没有强烈的区分。增加抑制剂的长度并没有显著提高效力。
