Lienkamp Karen, Madkour Ahmad E, Musante Ashlan, Nelson Christopher F, Nüsslein Klaus, Tew Gregory N
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Am Chem Soc. 2008 Jul 30;130(30):9836-43. doi: 10.1021/ja801662y. Epub 2008 Jul 1.
Synthetic Mimics of Antimicrobial Peptides (SMAMPs) imitate natural host-defense peptides, a vital component of the body's immune system. This work presents a molecular construction kit that allows the easy and versatile synthesis of a broad variety of facially amphiphilic oxanorbornene-derived monomers. Their ring-opening metathesis polymerization (ROMP) and deprotection provide several series of SMAMPs. Using amphiphilicity, monomer feed ratio, and molecular weight as parameters, polymers with 533 times higher selectivitiy (selecitviy = hemolytic concentration/minimum inhibitory concentration) for bacteria over mammalian cells were discovered. Some of these polymers were 50 times more selective for Gram-positive over Gram-negative bacteria while other polymers surprisingly showed the opposite preference. This kind of "double selectivity" (bacteria over mammalian and one bacterial type over another) is unprecedented in other polymer systems and is attributed to the monomer's facial amphiphilicity.
抗菌肽的合成模拟物（SMAMPs）模仿天然宿主防御肽，而天然宿主防御肽是人体免疫系统的重要组成部分。这项工作展示了一种分子构建工具包，可轻松、灵活地合成多种具有表面两亲性的氧杂降冰片烯衍生单体。它们的开环易位聚合（ROMP）和脱保护反应生成了多个系列的SMAMPs。以两亲性、单体进料比和分子量为参数，发现了对细菌的选择性（选择性=溶血浓度/最低抑菌浓度）比哺乳动物细胞高533倍的聚合物。其中一些聚合物对革兰氏阳性菌的选择性比对革兰氏阴性菌高50倍，而其他聚合物则出人意料地表现出相反的偏好。这种“双重选择性”（对细菌的选择性高于对哺乳动物细胞，以及对一种细菌类型的选择性高于另一种细菌类型）在其他聚合物体系中是前所未有的，这归因于单体的表面两亲性。
