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由ROMP制备的抗菌聚合物具有前所未有的选择性:一种分子构建套件方法

Karen Lienkamp¹, Ahmad E Madkour, Ashlan Musante

¹Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.

Journal of the American Chemical Society

|July 3, 2008

概括

研究人员开发了一套多功能分子套件,以创建抗微生物 (SMAMPs) 的合成模仿物. 这些新型聚合物表现出前所未有的双重选择性,针对细菌而不是人类细胞,并区分细菌类型.

科学领域:

聚合物化学聚合物化学
生物材料科学生物材料科学
免疫学免疫学免疫学

背景情况:

自然宿主防御对先天免疫非常重要.
合成模仿抗微生物 (SMAMPs) 提供治疗潜力.
开发通往SMAMP的多功能合成路线是一个持续的挑战.

研究的目的:

提出一种分子构造工具包,用于合成多种 facially amphiphilic oxanorbornene衍生的单体.
通过环开放转化聚合 (ROMP) 和降解保护来探索SMAMP的合成.
根据两性,单体比和分子量来研究SMAMP的结构-活性关系.

主要方法:

合成面部两的氧化甲基和甲基单体.
环开元化聚合 (ROMP) 用于制造聚合物链.
单体的去保护产生SMAMPs.
血液溶解活性和抗微生物最小抑制度 (MIC) 的评估.

主要成果:

使用开发的分子套件成功合成了各种各样的SMAMPs.
发现聚合物具有533倍的选择性对细菌比哺乳动物的细胞.
识别出具有50倍选择性的聚合物,这些聚合物对阳性比阴性细菌具有50倍的选择性,反之亦然.
展示了前所未有的"双重选择性",归因于面部两性.

结论:

分子构造套件使新型SMAMP的多功能和简单合成成为可能.
面部两性是实现SMAMP中高和差异性选择性的关键.
这些发现为开发向的抗微生物聚合物疗法开辟了新的途径.

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