Chierici Sabine, Jourdan Muriel, Figuet Melanie, Dumy Pascal
LEDSS UMR 5616 & ICMG-FR2607, Universite Joseph Fourier, BP 53, 38041, Grenoble cedex 9, France.
Org Biomol Chem. 2004 Sep 7;2(17):2437-41. doi: 10.1039/B408325C. Epub 2004 Aug 5.
The delta-conotoxin EVIA from the Conus ermineus venom, a recently characterized toxin, exhibits cis-trans isomerism of the Leu12-Pro13 bond associated with the triggering of its biological activity. In this paper we use the pseudoproline concept to target the presumed bioactive cis conformation. We report the design and the synthesis of loop 2 analogs from residue 8 to 18 containing either the cis-inducing Cys(PsiMe,MePro)13 unit or the natural proline residue. NMR studies in water and molecular modeling allowed us to identify the amide bond "locked" in a cis conformation for as in the suggested bioactive form of the natural toxin.
来自芋螺毒液的δ-芋螺毒素EVIA是一种最近鉴定出的毒素，其亮氨酸12-脯氨酸13键存在顺反异构现象，这与其生物活性的触发有关。在本文中，我们使用假脯氨酸概念来靶向假定的生物活性顺式构象。我们报告了从第8位到第18位残基的环2类似物的设计与合成，这些类似物含有顺式诱导的半胱氨酸（ΨMe，MePro）13单元或天然脯氨酸残基。在水中的核磁共振研究和分子模拟使我们能够确定如天然毒素假定生物活性形式那样以顺式构象“锁定”的酰胺键。
