BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Exp Parasitol. 2011 Aug;128(4):444-7. doi: 10.1016/j.exppara.2011.03.015. Epub 2011 Mar 31.
Nine vinyl ester tripeptides selective for inhibition of mammalian proteasome trypsin-like activity were tested for in vitro activity against Trypanosoma brucei. Interestingly, two compounds showed trypanocidal activity in the low micromolar range without displaying cytotoxicity against human cells. However, the compounds did not inhibit the trypsin-like activity of the trypanosome proteasome although their effect correlates with inactivation of the chymotrypsin-like activity. This finding shows that the inhibitor sensitivities between mammalian and trypanosome proteasome are distinct. This difference may be exploited for rational anti-trypanosomal drug development.
九种对哺乳动物蛋白酶体胰蛋白酶样活性具有抑制作用的乙烯酯三肽被测试了它们对布氏锥虫的体外活性。有趣的是，两种化合物在低微摩尔范围内表现出杀锥虫活性，而对人体细胞没有细胞毒性。然而，这些化合物并没有抑制锥虫蛋白酶体的胰蛋白酶样活性，尽管它们的作用与糜蛋白酶样活性的失活相关。这一发现表明，哺乳动物和锥虫蛋白酶体的抑制剂敏感性是不同的。这种差异可能被利用来进行合理的抗锥虫药物开发。
