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为什么有些固定化的 N-烷基化聚亚乙基亚胺在灭活流感病毒方面远远优于其他的?

Why do some immobilized N-alkylated polyethylenimines far surpass others in inactivating influenza viruses?

机构信息

Departments of †Chemistry, ‡Biology, and ∥Biological Engineering and §Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.

出版信息

Biomacromolecules. 2015 Jan 12;16(1):351-6. doi: 10.1021/bm5015427. Epub 2014 Dec 22.

DOI:10.1021/bm5015427
PMID:25486335
Abstract

A number of N-alkylated polyethylenimines (PEIs) were covalently attached to glass-slide surfaces, and their virucidal efficacies against three different strains of influenza viruses were examined quantitatively. The anti-influenza activities of the modified surfaces varied widely, with the most potent, immobilized N,N-hexyl,methyl-PEI and N,N-dodecyl,methyl-PEI, reducing the viral titer by over three logs (i.e., >99.9%). While the virucidal activities of the glass surfaces derivatized with N-alkylated PEIs displayed no discernible correlation with such surface properties as hydrophobicity, charge, protein affinity, roughness, adhesive interactions, and polymer-chain extension lengths, they exhibited a marginal correlation with the surface density of the quaternary ammonium group, as titrated by means of fluorescein binding. However, this correlation markedly improved (to the correlation coefficient of 0.97 with a two-tailed p value of 0.044) when the titration was instead carried out using a macromolecular conjugate, the dye coupled to the protein lysozyme, suggesting that the critical determinant of the virucidal activity is the density of the immobilized quaternary ammonium groups accessible to influenza virions.

摘要

将几种 N-烷基化的聚乙烯亚胺(PEI)共价连接到玻片表面,并定量检测它们对三种不同流感病毒株的病毒杀灭效果。修饰表面的抗流感活性差异很大,最有效的固定化 N,N-己基甲基-PEI 和 N,N-十二基甲基-PEI 将病毒滴度降低了三个对数以上(即>99.9%)。尽管用 N-烷基化 PEI 衍生的玻璃表面的病毒杀灭活性与疏水性、电荷、蛋白质亲和力、粗糙度、粘附相互作用和聚合物链延伸长度等表面性质没有明显的相关性,但它们与通过荧光素结合滴定的季铵基团的表面密度呈轻微相关性。然而,当使用与蛋白质溶菌酶偶联的染料进行滴定时,这种相关性显著改善(相关系数为 0.97,双侧 p 值为 0.044),这表明病毒杀灭活性的关键决定因素是可接触流感病毒的固定化季铵基团的密度。

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