Department of Chemical Engineering, Dankook University , Yongin 448-701, South Korea.
Langmuir. 2013 Nov 19;29(46):14214-21. doi: 10.1021/la4036985. Epub 2013 Nov 7.
Poly(ethylene glycol) (PEG)-grafted magainin 2 and tachyplesin I were simulated with lipid bilayers. In the simulations of PEGylated magainin 2 and tachyplesin I in water, both peptides are wrapped by PEG chains. The α-helical structure of PEGylated magainin 2 is broken in water, while the β-sheet of PEGylated tachyplesin I keeps stable, similar to the structural behavior of unPEGylated peptides, in agreement with experiments. Simulations of PEGylated peptides with lipid bilayers show that PEG chains block the electrostatic interaction between cationic residues of peptides and anionic phosphates of lipids, leading to the less binding of the peptide to the bilayer surface, which is observed more significantly for magainin 2 than for tachyplesin I. Since the random-coiled magainin 2 can be more completely covered by PEGs than does the β-sheet tachyplesin I, the PEGylation effect on the decreased binding is larger for magainin 2, showing the dependence of PEGylation on the peptide structure. These simulation findings qualitatively support the experimental observation of the different extents of the reduced membrane-permeabilizing activity for PEGylated magainin 2 and tachyplesin I.
聚乙二醇（PEG）接枝抗菌肽 2 和 tachyplesin I 与脂质双层进行了模拟。在 PEG 化抗菌肽 2 和 tachyplesin I 在水中的模拟中，两种肽都被 PEG 链包裹。PEG 化抗菌肽 2 的α-螺旋结构在水中被破坏，而 PEG 化 tachyplesin I 的β-折叠保持稳定，与未 PEG 化肽的结构行为相似，与实验结果一致。与脂质双层的 PEG 化肽的模拟表明，PEG 链阻止了肽的阳离子残基与脂质的阴离子磷酸之间的静电相互作用，导致肽与双层表面的结合减少，这种情况在抗菌肽 2 中比在 tachyplesin I 中更为明显。由于无规卷曲的抗菌肽 2 可以比β-折叠的 tachyplesin I 更完全地被 PEG 覆盖，因此 PEG 化对结合减少的影响在抗菌肽 2 中更大，表明 PEG 化对肽结构的依赖性。这些模拟结果定性地支持了实验观察到的 PEG 化抗菌肽 2 和 tachyplesin I 的膜通透性降低活性的不同程度。
