Institute of Microbial Chemistry, Tokyo, Tokyo 141-0021, Japan.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5839-42. doi: 10.1016/j.bmcl.2010.07.122. Epub 2010 Aug 1.
The structure-activity relationship of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Based on the structure of a previously reported boronate analog of tyropeptin (2), 41 derivatives, which have varying substructure at the N-terminal acyl moiety and P2 position, were synthesized. Among them, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward chymotryptic activity of proteasome and cytotoxicity, respectively. The replacement of the isopropyl group in the P2 side chain to H or Me had negligible effects on the biological activities examined in this study.
研究了蛋白酶体抑制剂酪蛋白肽硼酸衍生物的构效关系。基于先前报道的酪蛋白肽硼酸类似物（2）的结构，合成了 41 种具有不同 N 端酰基部分和 P2 位取代基的衍生物。其中，3-苯氧基苯甲酰胺 6 和 3-氟吡啶酰胺 22 对蛋白酶体的糜蛋白酶活性和细胞毒性表现出最强的抑制活性。在本研究中，P2 侧链中异丙基取代为 H 或 Me 对所研究的生物活性几乎没有影响。
