Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity

Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity
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DOI:
10.1016/j.chemphyslip.2010.03.009
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发表时间:
2010-06-01
影响因子:
3.4
通讯作者:
Hicks, Rickey P.
Hicks, Rickey P.
中科院分区:
生物学3区
文献类型:
--
作者:
Russell, Amanda L.;Kennedy, Anthony M.;Hicks, Rickey P.

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在我们的实验室中,我们开发了一系列抗微生物肽,其对原核细胞表现出优于真核细胞的选择性和效力(Hicks等人,2007年)。进行圆二色性(CD)、等温量热法(ITC)和钙黄绿素渗漏测定以确定代表性肽1(Ac-GF-Tic-Oic-GK-Tic-Oic-GF-Tic-Oic-GK-Tic-KKKK-CONH 2)与模型膜的脂质结合机制。POPC脂质体用作真核生物膜的简单模型,4:1 POPC:POPG脂质体用作原核生物膜的简单模型。CD、ITC和钙黄绿素渗漏数据清楚地表明化合物1通过非常不同的机制与两种不同的脂质体膜相互作用。与POPC:POPG(4:1摩尔比)脂质体相比,化合物1在POPC脂质体中表现出较弱的结合并诱导较少的钙黄绿素渗漏。与POPC的主要结合机制似乎限于表面相互作用,而与4:1 POPC:POPG的结合机制最可能涉及某种类型的孔形成。(C)2010爱思唯尔爱尔兰有限公司版权所有。
In our laboratory we developed a series of antimicrobial peptides that exhibit selectivity and potency for prokaryotic over eukaryotic cells (Hicks et al., 2007). Circular dichroism (CD), isothermal calorimetry (ITC) and calcein leakage assays were conducted to determine the mechanism of lipid binding of a representative peptide 1 (Ac-GF-Tic-Oic-GK-Tic-Oic-GF-Tic-Oic-GK-Tic-KKKK-CONH2) to model membranes. POPC liposomes were used as a simple model for eukaryotic membranes and 4:1 POPC:POPG liposomes were used as a simple model for prokaryotic membranes. CD, ITC and calcein leakage data clearly indicate that compound 1 interacts via very different mechanisms with the two different liposome membranes. Compound 1 exhibits weaker binding and induces less calcein leakage in POPC liposomes than POPC:POPG (4:1 mole ratio) liposomes. The predominant binding mechanism to POPC appears to be limited to surface interactions while the mechanism of binding to 4:1 POPC:POPG most likely involves some type of pore formation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.