科學(xué)家開發(fā)出了一類抑制劑,，它們可以螯合并中和細(xì)菌毒素,，這在標(biāo)準(zhǔn)的抗生素基礎(chǔ)上帶來了顯著的改善,?？股貧⑺兰?xì)胞并常常讓細(xì)菌毒素釋放進血流中,。這些新的抑制劑和傳統(tǒng)療法聯(lián)合使用可以對許多種產(chǎn)生可溶性毒素的細(xì)菌有效,，例如腸出血性大腸桿菌O157：H7——這種細(xì)菌通常是食物中毒暴發(fā)的元兇。
David Bundle及其同事設(shè)計出了一種聚合物骨架,，它可以把大腸桿菌O157：H7的志賀毒素和一種血漿蛋白——人類正五聚蛋白中的血清淀粉樣蛋白P（HuSAP）聚集起來,，后者是先天免疫系統(tǒng)的一個成分。這種毒素和免疫蛋白都含有弱結(jié)合伙伴（或稱配體）,，沒有這些配體他們就無法發(fā)揮功能,。這組作者準(zhǔn)確地讓聚合物骨架上的這些配體吸引并捕獲了目標(biāo)毒素以及能消滅它們的免疫蛋白。這種新的抑制劑被稱為(S)-PolyBAIT,，它能保護表達HuSAP的小鼠不受中毒劑量的志賀毒素的影響,，后者可以導(dǎo)致大腸桿菌中毒病例常見的溶血性尿毒癥綜合征。這組科學(xué)家說,，(S)-PolyBAIT促進了穩(wěn)定的毒素-HuSAP絡(luò)合物的形成,，并引導(dǎo)它們被清除掉。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
