Sarubbi E, Seneci P F, Angelastro M R, Peet N P, Denaro M, Islam K
Lepetit Research Center, MMDRI, Gerenzano, VA, Italy.
FEBS Lett. 1993 Mar 22;319(3):253-6. doi: 10.1016/0014-5793(93)80557-b.
We have recently shown that alpha-MAPI, a peptidic aldehyde of microbial origin, inhibits the HIV protease with a potency comparable to pepstatin, having, differently from pepstatin, no activity on other aspartic proteases. In this study different peptide derivatives containing a C-terminal aldehyde have been tested to assess the potential of this function for the inhibition of HIV protease. The results of our analysis correspond with the recently published subsite preferences of the viral enzyme, indicating that aldehydes bind to the active site of the HIV protease. Our data suggest that peptide aldehydes can act in their hydrated forms as transition state analogues with the most potent inhibitor having an IC50 of 0.9 microM.
我们最近发现，α-MAPI是一种源自微生物的肽醛，它对HIV蛋白酶的抑制效力与胃蛋白酶抑制剂相当，与胃蛋白酶抑制剂不同的是，它对其他天冬氨酸蛋白酶没有活性。在本研究中，我们测试了不同的含有C端醛基的肽衍生物，以评估这种官能团对HIV蛋白酶的抑制潜力。我们的分析结果与最近发表的该病毒酶的亚位点偏好性相符，表明醛基与HIV蛋白酶的活性位点结合。我们的数据表明，肽醛可以以其水合形式作为过渡态类似物起作用，其中最有效的抑制剂的IC50为0.9微摩尔。
