科学家开发出了一类抑制剂，它们可以螯合并中和细菌毒素，这在标准的抗生素基础上带来了显著的改善。抗生素杀死细胞并常常让细菌毒素释放进血流中。这些新的抑制剂和传统疗法联合使用可以对许多种产生可溶性毒素的细菌有效，例如肠出血性大肠杆菌O157：H7——这种细菌通常是食物中毒暴发的元凶。
David Bundle及其同事设计出了一种聚合物骨架，它可以把大肠杆菌O157：H7的志贺毒素和一种血浆蛋白——人类正五聚蛋白中的血清淀粉样蛋白P（HuSAP）聚集起来，后者是先天免疫系统的一个成分。这种毒素和免疫蛋白都含有弱结合伙伴（或称配体），没有这些配体他们就无法发挥功能。这组作者准确地让聚合物骨架上的这些配体吸引并捕获了目标毒素以及能消灭它们的免疫蛋白。这种新的抑制剂被称为(S)-PolyBAIT，它能保护表达HuSAP的小鼠不受中毒剂量的志贺毒素的影响，后者可以导致大肠杆菌中毒病例常见的溶血性尿毒症综合征。这组科学家说，(S)-PolyBAIT促进了稳定的毒素-HuSAP络合物的形成，并引导它们被清除掉。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS published October 27, 2008, doi:10.1073/pnas.0804919105
In vivo supramolecular templating enhances the activity of multivalent ligands: A potential therapeutic against the Escherichia coli O157 AB5 toxins
Pavel I. Kitov, George L. Mulvey, Thomas P. Griener, Tomasz Lipinski, Dmitry Solomon, Eugenia Paszkiewicz, Jared M. Jacobson, Joanna M. Sadowska, Missao Suzuki, Ken-ichi Yamamura, Glen D. Armstrong, and David R. Bundle
We demonstrate that interactions between multimeric receptors and multivalent ligands are dramatically enhanced by recruiting a complementary templating receptor such as an endogenous multimeric protein but only when individual ligands are attached to a polymer as preorganized, covalent, heterobifunctional pairs. This effect cannot be replicated by a multivalent ligand if the same recognition elements are independently arrayed on the scaffold. Application of this principle offers an approach to create high-avidity inhibitors for multimeric receptors. Judicious selection of the ligand that engages the templating protein allows appropriate effector function to be incorporated in the polymeric construct, thereby providing an opportunity for therapeutic applications. The power of this approach is exemplified by the design of exceptionally potentEscherichia coli Shiga toxin antagonists that protect transgenic mice that constitutively express a human pentraxin, serum amyloid P component.
