Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden.
J Phys Chem B. 2010 Jun 3;114(21):7207-15. doi: 10.1021/jp1016664.
The effect of charge density on the interaction between cationic peptides and oppositely charged poly(acrylic acid-co-acrylamide) microgels was investigated together with effects of charge localization and interplay between electrostatic and hydrophobic interactions. The microgel charge content was controlled by varying acrylic acid/acrylamide ratios (25/75-100/0 mol %) in the microgel synthesis, whereas peptide charge density was controlled by using monodisperse peptides containing alanine and lysine in a series of repeated patterns (25-50 mol % lysine). Results show that peptide uptake in the microgels is largely determined by microgel charge density, whereas peptide-induced microgel deswelling kinetics is influenced by peptide charge density to a higher degree. Furthermore, electrolyte-induced peptide detachment is highly influenced by both microgel and peptide charge density. Thus, at high charge contrast, peptides could not be detached from the microgels, whereas reducing the charge density of either peptide or microgel promoted electrolyte-induced peptide release. The localization of charges in the peptide sequence also plays a significant role as the interaction strength increased for peptides where all charged groups are located at the end of the sequence, as opposed to homogenously distributed throughout the peptide. Such an asymmetrically charged peptide thus displayed higher uptake, faster deswelling response, and lower release degrees than its homogeneously charged analogue in microgels with high charge content, while these differences were absent for lower microgel charge densities. Hydrophobic substitutions (alanine --> leucine) in the peptide chain at fixed charge content increased peptide binding strength and eliminated peptide detachment at high ionic strength. Theoretical modeling of the effect of peptide and microgel charge density on peptide-induced microgel deswelling gave good agreement with experimental results.
研究了阳离子肽与带相反电荷的聚（丙烯酸-co-丙烯酰胺）微凝胶之间的相互作用受电荷量密度的影响，以及电荷定位和静电相互作用与疏水相互作用之间的相互作用的影响。通过改变微凝胶合成中的丙烯酸/丙烯酰胺比（25/75-100/0mol%）来控制微凝胶的电荷含量，而通过使用含丙氨酸和赖氨酸的一系列重复模式（25-50mol%赖氨酸）的单分散肽来控制肽的电荷量密度。结果表明，肽在微凝胶中的摄取主要由微凝胶的电荷量密度决定，而肽诱导的微凝胶溶胀动力学受肽电荷量密度的影响更大。此外，电解质诱导的肽释放受微凝胶和肽电荷量密度的共同影响。因此，在高电荷对比下，肽不能从微凝胶中脱离，而降低肽或微凝胶的电荷量密度则促进了电解质诱导的肽释放。肽序列中电荷的定位也起着重要作用，因为当所有带电荷的基团都位于序列的末端时，序列中的相互作用强度增加，而不是均匀分布在整个肽中。与在高电荷含量的微凝胶中具有均匀电荷分布的类似物相比，这种带不对称电荷的肽具有更高的摄取量、更快的溶胀响应和更低的释放程度，而在较低的微凝胶电荷密度下则没有这些差异。在固定电荷含量下，肽链中的疏水性取代（丙氨酸→亮氨酸）增加了肽结合强度，并在高离子强度下消除了肽的脱离。肽和微凝胶电荷量密度对肽诱导的微凝胶溶胀的影响的理论模型与实验结果吻合良好。
