Baldisserotto Anna, Marastoni Mauro, Lazzari Ilaria, Trapella Claudio, Gavioli Riccardo, Tomatis Roberto
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Ferrara, Italy.
Eur J Med Chem. 2008 Jul;43(7):1403-11. doi: 10.1016/j.ejmech.2007.10.002. Epub 2007 Oct 7.
Here we report the synthesis and biological properties of peptide-based molecules bearing constrained analogues of phenylalanine at the C-terminal. Compounds were tested as proteasome subunits' inhibitors. Dehydro-peptides showed good inhibition, in particular against trypsin-like (T-L) proteasome activity while some C-terminal Tic-derivatives inhibit only caspase-like activity in enzymatic beta1 subunits with a certain degree of efficacy. The best analogues of the series demonstrated good resistance to proteolysis and a capacity to permeate the cell membrane.
在此，我们报告了在C端带有苯丙氨酸受限类似物的肽基分子的合成及其生物学特性。这些化合物作为蛋白酶体亚基抑制剂进行了测试。脱氢肽表现出良好的抑制作用，尤其是对胰蛋白酶样（T-L）蛋白酶体活性，而一些C端Tic衍生物仅对酶促β1亚基中的半胱天冬酶样活性具有一定程度的有效抑制作用。该系列中最佳的类似物表现出对蛋白水解的良好抗性以及穿透细胞膜的能力。
