Cationic Side Chain Identity Directs the Hydrophobically Driven Self-Assembly of Amphiphilic β-Peptides in Aqueous Solution
Cationic Side Chain Identity Directs the Hydrophobically Driven Self-Assembly of Amphiphilic β-Peptides in Aqueous Solution
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DOI：
10.1021/acs.langmuir.0c03255
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发表时间：
2021-03-08
期刊：
影响因子：
3.9
通讯作者：
Abbott, Nicholas L.
中科院分区：
文献类型：
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作者：
Wang, Chenxuan;Biok, Naomi A.;Abbott, Nicholas L.
水中非极性分子片段介导的疏水相互作用受到局部化学和物理环境的影响，其影响方式尚不完全清楚。在这里，我们使用具有稳定构象的全局两亲性 (GA) β-肽（GA-Lys 和 GA-Arg）来探索用 β(3)-高精氨酸 (β Arg) 替换 β(3)-高赖氨酸 (β Lys) 是否会影响这些肽在大量水溶液中的疏水驱动组装。研究在 pH 7 的 10 mM 三乙醇胺缓冲液中进行，其中 β Lys（铵）和 β Arg（胍）侧链均显着质子化。添加 60 vol% MeOH 之前和之后的光散射测量和冷冻电子显微照片的比较表明，AcY-GA-Lys 与 AcY-GA-Arg 的疏水驱动组装结果非常不同（AcY 表示每个 N 末端的 N-乙酰化 -β(3)-高酪氨酸 (β Tyr)）。核磁共振和分析超速离心证实 AcY-GA-Lys 在水性缓冲液中组装成大聚集体，而类似浓度的 AcY-GA-Arg 仅形成小寡聚物。将 AcY-GA-Arg 滴定到 AcY-GA-Lys 水溶液中表明，AcY-GA-Lys 缔合的驱动力远强于 AcY-GA-Arg 缔合的驱动力。我们根据过去的实验观察讨论这些结果，涉及使用 GA β 肽进行单分子力测量，以及疏水驱动的常规肽二聚化，这些传统肽在二聚化后形成 GA α 螺旋（但不显示通过使用 β 肽进行的早期 AFM 研究推断得出的 Lys 与 Arg 趋势）。总体而言，我们的结果表明，近端阳离子基团（铵与胍）的特性深刻地调节了本体水溶液中构象稳定的β-肽的疏水驱动自组装。
Hydrophobic interactions mediated by nonpolar molecular fragments in water are influenced by local chemical and physical contexts in ways that are not yet fully understood. Here, we use globally amphiphilic (GA) beta-peptides (GA-Lys and GA-Arg) with stable conformations to explore if replacement of beta(3)-homolysine (beta Lys) with beta(3)-homoarginine (beta Arg) influences the hydrophobically driven assembly of these peptides in bulk aqueous solution. The studies were conducted in 10 mM triethanolamine buffer at pH 7, where both beta Lys (ammonium) and beta Arg (guanidinium) side chains are substantially protonated. Comparisons of light scattering measurements and cryo-electron micrographs before and after the addition of 60 vol% MeOH indicate very different outcomes of the hydrophobically driven assembly of AcY-GA-Lys versus AcY-GA-Arg (AcY denotes an N-acetylated-beta(3)-homotyrosine (beta Tyr) at each N-terminus). Nuclear magnetic resonance and analytical ultracentrifugation confirm that AcY-GA-Lys assembles into large aggregates in aqueous buffer, whereas AcY-GA-Arg at comparable concentrations forms only small oligomers. Titration of AcY-GA-Arg into aqueous solutions of AcY-GA-Lys reveals that the driving force for AcY-GA-Lys association is far stronger than that for AcY-GA-Arg association. We discuss these results in the light of past experimental observations involving single molecule force measurements with GA beta-peptides and hydrophobically driven dimerization of conventional peptides that form a GA alpha-helix upon dimerization (but do not display the Lys versus Arg trend predicted by extrapolating from the earlier AFM studies with beta-peptides). Overall, our results establish that the identity of proximal cationic groups, ammonium versus guanidinium, profoundly modulates the hydrophobically driven self-assembly of conformationally stable beta-peptides in bulk aqueous solution.