Galleria mellonella native and analogue peptides Gm1 and ΔGm1. I) Biophysical characterization of the interaction mechanisms with bacterial model membranes

Galleria mellonella native and analogue peptides Gm1 and ΔGm1. I) Biophysical characterization of the interaction mechanisms with bacterial model membranes
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DOI:
10.1016/j.bbamem.2014.07.006
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发表时间:
2014-10-01
影响因子:
3.4
通讯作者:
Brandenburg, Klaus
Brandenburg, Klaus
中科院分区:
生物学3区
文献类型:
--
作者:
Correa, Wilmar;Manrique-Moreno, Marcela;Brandenburg, Klaus

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天然抗菌肽是动植物天然免疫系统的重要组成部分。它们被认为是传统抗生素的有前途的替代品。在这里,我们提出了一个比较研究的两个合成肽:Gm 1,对应于自然的整体不带电荷的肽从大蜡螟(Gm)和三角洲Gm 1,一个修改的整体带正电荷的Gm 1变体。我们利用傅里叶变换红外光谱(FTIR)、Forster共振能量转移光谱(FRET)、差示扫描量热法(DSC)和等温滴定量热法(ITC)。GM 1产生不稳定的影响凝胶液晶相变的酰基链的脂质,推导出从相变温度和焓的降低,这表明流化,而Δ GM 1导致相反的行为。此外,FTIR分析的功能基团的脂质参与与肽的相互作用表明,在频带的位置和强度的不对称的PO 2-伸缩振动源自脂质磷酸盐基团,在头部基团区域的空间变化的结果的移位。有趣的是,FRET光谱显示两种肽类似地嵌入DMPG和LPS中,但更少地嵌入DMPE膜系统中。这些结果进行了讨论,根据可能使用的肽作为抗微生物和抗内毒素药物。(C)2014爱思唯尔有限公司版权所有。
Natural occurring antimicrobial peptides (AMPs) are important components of the innate immune system of animals and plants. They are considered to be promising alternatives to conventional antibiotics. Here we present a comparative study of two synthetic peptides: Gm1, corresponding to the natural overall uncharged peptide from Galleria mellonella (Gm) and Delta Gm1, a modified overall positively charged Gm1 variant. We have studied the interaction of the peptides with lipid membranes composed of different kinds of lipopolysaccharides (LPS) and dimyristoylphosphatidylglycerol (DMPG), in some cases also dimyristoylphosphatidylethanolamine (DMPE) as representative lipid components of Gram-negative bacterial membranes, by applying Fourier-transform infrared spectroscopy (FTIR), Forster resonance energy transfer spectroscopy (FRET), differential scanning calorimety (DSC) and isothermal titration calorimetry (ITC). Gm1 generates a destabilizing effect on the gel to liquid crystalline phase transition of the acyl chains of the lipids, as deduced from a decrease in the phase transition temperature and enthalpy, suggesting a fluidization, whereas Delta Gm1 led to the opposite behavior. Further, FTIR analysis of the functional groups of the lipids participating in the interaction with the peptides indicated a shift in the band position and intensity of the asymmetric PO2- stretching vibration originating from the lipid phosphate groups, a consequence of the sterical changes in the head group region. Interestingly, FRET spectroscopy showed a similar intercalation of both peptides into the DMPG and LPS, but much less into the DMPE membrane systems. These results are discussed in the light of a possible use of the peptides as antimicrobial and anti-endotoxin drugs. (C) 2014 Elsevier B.V. All rights reserved.