Paramonov Sergey E, Jun Ho-Wook, Hartgerink Jeffrey D
Department of Chemistry, Rice University, 6100 Main Street, MS60, Houston, Texas 77005, USA.
J Am Chem Soc. 2006 Jun 7;128(22):7291-8. doi: 10.1021/ja060573x.
The role of hydrogen bonding and amphiphilic packing in the self-assembly of peptide-amphiphiles (PAs) was investigated using a series of 26 PA derivatives, including 19 N-methylated variants and 7 alanine mutants. These were studied by circular dichroism spectroscopy, a variety of Fourier transform infrared spectroscopies, rheology, and vitreous ice cryo-transmission electron microscopy. From these studies, we have been able to determine which amino acids are critical for the self-assembly of PAs into nanofibers, why the nanofiber is favored over other possible nanostructures, the orientation of hydrogen bonding with respect to the nanofiber axis, and the constraints placed upon the portion of the peptide most intimately associated with the biological environment. Furthermore, by selectively eliminating key hydrogen bonds, we are able to completely change the nanostructure resulting from self-assembly in addition to modifying the macroscopic mechanical properties associated with the assembled gel. This study helps to clarify the mechanism of self-assembly for peptide amphiphiles and will thereby help in the design of future generations of PAs.
使用一系列26种肽两亲物（PA）衍生物，包括19种N-甲基化变体和7种丙氨酸突变体，研究了氢键和两亲性堆积在肽两亲物（PA）自组装中的作用。通过圆二色光谱、多种傅里叶变换红外光谱、流变学和玻璃态冰冷冻透射电子显微镜对这些进行了研究。通过这些研究，我们能够确定哪些氨基酸对于PA自组装成纳米纤维至关重要，为什么纳米纤维比其他可能的纳米结构更受青睐，氢键相对于纳米纤维轴的取向，以及对与生物环境最密切相关的肽部分所施加的限制。此外，通过选择性消除关键氢键，我们不仅能够改变与组装凝胶相关的宏观力学性能，还能够完全改变自组装产生的纳米结构。这项研究有助于阐明肽两亲物的自组装机制，从而有助于下一代PA的设计。
