Yin Zheng, Patel Sejal J, Wang Wei-Ling, Chan Wai-Ling, Ranga Rao K R, Wang Gang, Ngew Xinyi, Patel Viral, Beer David, Knox John E, Ma Ngai Ling, Ehrhardt Claus, Lim Siew Pheng, Vasudevan Subhash G, Keller Thomas H
Novartis Institute for Tropical Diseases, 10 Biopolis Road, 05-01 Chromos, 138670 Singapore.
Bioorg Med Chem Lett. 2006 Jan 1;16(1):40-3. doi: 10.1016/j.bmcl.2005.09.049. Epub 2005 Oct 21.
With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K(i)=5.8 microM). In general, we observe that interactions of P(2) side chain are more important than P(1) followed by P(3) and P(4). Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P(1) Arg is identified.
为了发现强效且具有选择性的登革热NS3蛋白酶抑制剂，我们基于先导醛1（Bz-Nle-Lys-Arg-Arg-H，K(i)=5.8微摩尔）系统地合成并评估了一系列四肽醛。总体而言，我们观察到P(2)侧链的相互作用比P(1)更重要，其次是P(3)和P(4)。三肽和二肽醛抑制剂也显示出低微摩尔活性。此外，还确定了一种有效的P(1)精氨酸的非碱性、不带电荷的替代物。
