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首页> 外文期刊>Biochemistry >Limiting an Antimicrobial Peptide to the Lipid−Water Interface Enhances Its Bacterial Membrane Selectivity: A Case Study of MSI-367
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Limiting an Antimicrobial Peptide to the Lipid−Water Interface Enhances Its Bacterial Membrane Selectivity: A Case Study of MSI-367

机译：将抗菌肽限制在脂质-水界面上可增强其细菌膜选择性：以MSI-367为例

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摘要

In a minimalist design approach, a synthetic peptideMSI-367 [(KFAKKFA)3-NH2] was designednand synthesized with the objective of generating cell-selective nonlytic peptides, which have a significant bearing onncell targeting. The peptide exhibited potent activity against both bacteria and fungi, but no toxicity to human cells atnmicromolar concentrations. Bacterial versus human cell membrane selectivity of the peptide was determined vianmembrane permeabilization assays. Circular dichroism investigations revealed the intrinsic helix propensity of thenpeptide, β-turn structure in aqueous buffer and extended and turn conformations upon binding to lipid vesicles.nDifferential scanning calorimetry experiments with 1,2-dipalmitoleoyl-sn-glycero-3-phosphatidylethanolaminenbilayers indicated the induction of positive curvature strain and repression of the fluid lamellar to invertednhexagonal phase transition by MSI-367. Results of isothermal titration calorimetry (ITC) experiments suggestednthe possibility of formation of specific lipid-peptide complexes leading to aggregation.n2nH nuclear magneticnresonance (NMR) of deuterated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) multilamellarnvesicles confirmed the limited effect of the membrane-embedded peptide at the lipid-water interface.n31nPNMRndata indicated changes in the lipid headgroup orientation of POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospha-ntidylglycerol, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine lipid bilayers upon peptide bind-ning. Membrane-embedded and membrane-inserted states of the peptide were observed via sum frequencyngeneration vibrational spectroscopy. Circular dichroism, ITC, and 31nPNMRdatafor Escherichia coli lipids agreenwith the hypothesis that strong electrostatic lipid-peptide interactions embrace the peptide at the lipid-waterninterface and provide the basis for bacterial cell selectivity.
机译：在极简设计方法中，设计并合成了合成肽MSI-367 [（KFAKKFA）3-NH2]，目的是生成细胞选择性非溶解性肽，其对细胞定向具有重要意义。该肽对细菌和真菌均显示出有效的活性，但在微摩尔浓度下对人细胞无毒性。通过膜通透测定法测定了肽对细菌和人细胞膜的选择性。圆二色性研究揭示了内肽的内在螺旋倾向，在水性缓冲液中的β-转向结构以及与脂质囊泡结合后的延伸和转向构象。n用1,2-二棕榈油酰基-sn-甘油-3-磷脂酰乙醇胺双分子层的差示扫描量热法实验表明诱导MSI-367对正曲率应变和流体层状向逆六方相变的抑制作用。等温滴定热法（ITC）实验的结果表明，可能形成特定的脂肽复合物导致聚集。氘化的1-棕榈酰基-2-油酰基-sn-甘油-3-磷脂酰胆碱（POPC）多层小泡的n2nH核磁共振（NMR）。证实膜包埋的肽在脂质-水界面上的作用有限。n31nPNMRn数据表明，POPC，1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸-吡啶基甘油和1-棕榈酰基的脂质头基方向变化肽结合后，-2-油基-sn-甘油-3-磷脂酰乙醇胺脂质双层。通过和频发生振动光谱法观察该肽的膜嵌入状态和膜插入状态。大肠埃希氏菌脂质的圆二色性，ITC和31nPNMR数据呈绿色，假说是强的静电脂质-肽相互作用在脂质-水界面上包含了肽，并为细菌细胞选择性提供了基础。

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  • 来源
    《Biochemistry》 |2010年第50期|p.10595-10605|共11页
  • 作者

    Sathiah Thennarasu Rui Huang Dong-Kuk Lee Pei Yang Lee Maloy Zhan Chen and Ayyalusamy Ramamoorthy;

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    ‡Department of Biophysics, and §Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055,United States,) Genaera Pharmaceuticals, Plymouth Meeting, Pennsylvania 19462, United States.^Present address: OrganicChemistry Laboratory, Central Leather Research Institute, Adayaru, Chennai 600 020, India, andPresent address:Department of FineChemistry, SeoulNationalUniversity of Technology, Seoul,Korea 139-743.;

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