Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes.
Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes.
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DOI：
10.1016/j.bbamem.2014.05.022
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
Gidalevitz, David
中科院分区：
文献类型：
--
作者：
Andreev, Konstantin;Bianchi, Christopher;Laursen, Jonas S.;Citterio, Linda;Hein-Kristensen, Line;Gram, Lone;Kuzmenko, Ivan;Olsen, Christian A.;Gidalevitz, David
关键词：
一类有前途的潜在新抗生素是抗菌肽或其合成模拟物。在这里，我们评估了阳离子侧链类型的影响（即，胍基与氨基）对抗微生物α-肽-β-类肽嵌合体的膜扰动机制的影响。两个单独的Langmuir单分子膜组成的1，2-二棕榈酰-sn-甘油-3-磷脂酰甘油（DPPG）和脂多糖Kdo 2-脂质A分别模拟革兰氏阳性和革兰氏阴性细菌的外膜。我们报告的测量结果，使用一系列的技术，包括高分辨率同步辐射表面X射线散射，落射荧光显微镜，并在体外抗菌活性，研究肽模拟物与细菌膜相互作用的分子机制。我们发现，含胍基的嵌合体表现出更大的破坏性活动DPPG单层比含氨基的类似物。然而，在脂多糖单层中没有观察到这种效应，其中差异可以忽略不计。此外，硝基苯并恶二唑荧光团的加入并没有降低这些抗菌剂插入到两个模型膜系统检查，这可能是有用的，为未来的细胞定位研究的活性。
A promising class of potential new antibiotics are the antimicrobial peptides or their synthetic mimics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide–β-peptoid chimeras. Two separate Langmuir monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) and lipopolysaccharide Kdo2-lipid A were applied to model the outer membranes of Gram-positive and Gram-negative bacteria, respectively. We report the results of the measurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecular mechanisms of peptidomimetic interaction with bacterial membranes. We found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPG monolayers than the amino group-containing analogues. However, this effect was not observed for lipopolysaccharide monolayers where the difference was negligible. Furthermore, the addition of the nitrobenzoxadiazole fluorophore did not reduce the insertion activity of these antimicrobials into both model membrane systems examined, which may be useful for future cellular localization studies.
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影响因子：
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