Buettner C J, Wallace A J, Ok S, Manos A A, Nicholl M J, Ghosh A, Tweedle M F, Goldberger J E
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Org Biomol Chem. 2017 Jun 21;15(24):5220-5226. doi: 10.1039/c7ob00875a.
While the influence of alkyl chain length and headgroup size on self-assembly behaviour has been well-established for simple surfactants, the rational control over the pH- and concentration-dependent self-assembly behaviour in stimuli responsive peptides remains an elusive goal. Here, we show that different amphiphilic peptides can have similar self-assembly phase diagrams, providing the relative strengths of the attractive and repulsive forces are balanced. Using palmitoyl-YYAAEEEEK(DO3A:Gd)-NH and palmitoyl-YAAEEEEK(DO3A:Gd)-NH as controls, we show that reducing hydrophobic attractive forces through fewer methylene groups in the alkyl chain will lead to a similar self-assembly phase diagram as increasing the electrostatic repulsive forces via the addition of a glutamic acid residue. These changes allow creation of self-assembled MRI vehicles with slightly different micelle and nanofiber diameters but with minimal changes in the spin-lattice T relaxivity. These findings reveal a powerful strategy to design self-assembled vehicles with different sizes but with similar self-assembly profiles.
虽然对于简单表面活性剂而言，烷基链长度和头基大小对自组装行为的影响已得到充分证实，但在刺激响应性肽中，对pH和浓度依赖性自组装行为进行合理控制仍是一个难以实现的目标。在此，我们表明，只要吸引力和排斥力的相对强度达到平衡，不同的两亲性肽可以具有相似的自组装相图。以棕榈酰-YYAAEEEEK(DO3A:Gd)-NH和棕榈酰-YAAEEEEK(DO3A:Gd)-NH作为对照，我们发现，通过减少烷基链中亚甲基的数量来降低疏水吸引力，会导致与通过添加谷氨酸残基增加静电排斥力相似的自组装相图。这些变化使得能够创建具有略有不同的胶束和纳米纤维直径，但自旋晶格T弛豫率变化最小的自组装MRI载体。这些发现揭示了一种强大的策略，可用于设计具有不同尺寸但具有相似自组装轮廓的自组装载体。
