The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
Bioorg Med Chem Lett. 2013 Sep 1;23(17):4892-5. doi: 10.1016/j.bmcl.2013.06.086. Epub 2013 Jul 6.
μ-Conotoxin KIIIA blocks voltage-gated sodium channels and displays potent analgesic activity in mice models for pain. Structure-activity studies with KIIIA have shown that residues important for sodium channel activity are presented on an α-helix. Herein, we report the de novo design and synthesis of a three-residue (Lys7, Trp8, His12) peptidomimetic based on a novel diketopiperazine (DKP) carboxamide scaffold.
μ-芋螺毒素 KIIIA 可阻断电压门控钠离子通道，并在用于疼痛的小鼠模型中显示出强大的镇痛活性。对 KIIIA 的结构-活性研究表明，对钠通道活性重要的残基位于 α-螺旋上。在此，我们报告了一种基于新型二酮哌嗪（DKP）羧酰胺支架的三残基（Lys7、Trp8、His12）肽模拟物的从头设计和合成。
