Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University , 1-3 Machikaneyamacho, Toyonaka, Osaka 560-8531, Japan.
J Phys Chem B. 2017 Oct 5;121(39):9213-9222. doi: 10.1021/acs.jpcb.7b04007. Epub 2017 Sep 27.
Bilayer vesicles have garnered considerable research attention as molecular vehicles capable of noncovalent interaction with biomolecules via electrostatic and hydrophobic bonds and van der Waals interactions. Guanidinium strongly interacts with phosphate groups. Thus, guanidinium modification of vesicles helps intensify the interaction between lipid membranes and nucleic acids. Here, two kinds of guanidinium derivatives, stearylguanidinium (SG) and myristoylarginine (MA), were synthesized and incorporated into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) vesicles. Differences in their membrane properties were evaluated using Fourier transform infrared spectroscopy, Raman spectroscopy, and the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH), 6-lauroyl-2-dimethylaminonaphthalene (Laurdan), and 2-p-toluidinylnaphthalene-6-sulfonate (TNS). The increased SG ratio increased overall hydrophobicity and lipid packing density compared to POPC vesicles, and SG-modified vesicles successfully attracted and then denatured negatively charged tRNAs (tRNAs). In contrast, MA-modified vesicles did not affect the stiffness of POPC membranes, wherein no conformational change in tRNAs was observed in the presence of POPC/MA vesicles. Analyses of the pH-dependent fluorescence emission of TNS suggested that SG and MA molecules render the membrane surfaces cationic and anionic, respectively, which was also revealed by zeta potential measurements. Our results enabled the construction of a model of the headgroup orientation of zwitterionic POPC molecules controlled by modification with guanidinium derivatives. The results also indicate the possibility to regulate the interaction and conformation of biological molecules, such as nucleic acid.
双层囊泡作为分子载体，能够通过静电和疏水键以及范德华相互作用与生物分子进行非共价相互作用，引起了相当多的研究关注。胍基强相互作用于磷酸基团。因此，囊泡的胍基修饰有助于增强脂质膜与核酸之间的相互作用。在这里，合成了两种胍基衍生物，硬脂酰胍（SG）和肉豆蔻酰精氨酸（MA），并将其掺入 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）囊泡中。使用傅里叶变换红外光谱、拉曼光谱和荧光探针 1,6-二苯基-1,3,5-己三烯（DPH）、6-月桂酰基-2-二甲基氨基萘（Laurdan）和 2-对甲苯胺基萘-6-磺酸（TNS）评估了它们的膜性质差异。与 POPC 囊泡相比，SG 比例增加会增加整体疏水性和脂质堆积密度，并且 SG 修饰的囊泡成功地吸引并变性带负电荷的 tRNA（tRNA）。相比之下，MA 修饰的囊泡不会影响 POPC 膜的刚性，在存在 POPC/MA 囊泡的情况下，tRNA 没有观察到构象变化。TNS 的 pH 依赖性荧光发射分析表明，SG 和 MA 分子分别使膜表面带正电荷和负电荷，这也通过 ζ 电位测量得到证实。我们的结果使构建受胍基衍生物修饰控制的两性离子 POPC 分子的头基取向模型成为可能。结果还表明，有可能调节生物分子（如核酸）的相互作用和构象。
