Rajbhandary Annada, Nilsson Bradley L
Department of Chemistry, University of Rochester, Rochester, New York.
Biopolymers. 2017 Mar;108(2). doi: 10.1002/bip.22994.
Low molecular weight agents that undergo self-assembly into fibril networks with hydrogel properties are promising biomaterials. Most low molecular weight hydrogelators are discovered empirically or serendipitously due to imperfect understanding of the mechanisms of self-assembly, the packing structure of self-assembled materials, and how the self-assembly process corresponds to emergent hydrogelation. Herein, the mechanisms of self-assembly and hydrogelation of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-PhePhe), a well-studied low molecular weight hydrogelator, is probed by systematic comparison with derivatives in which Phe residues are replaced by corresponding N-benzyl glycine peptoid (Nphe) analogs. Peptoids are peptidomimetics that shift display of side chain functionality from the α-carbon to the terminal nitrogen. This alters the hydrogen bonding capacity, the side chain presentation geometry, amide cis/trans isomerization equilibrium, and β-sheet potential of the peptoid relative to the corresponding amino acid in the context of peptidic polymers. It was found that amino acid/peptoid hybrids Fmoc-Phe-Nphe and Fmoc-Nphe-Phe have altered fibril self-assembly propensity and reduced hydrogelation capacity relative to the parent dipeptide, and that fibril self-assembly of the dipeptoid, Fmoc-Nphe-Nphe, is completely curtailed. These findings provide insight into the potential of low molecular weight peptoids and peptide/peptoid hybrids as hydrogelation agents and illuminate the importance of hydrogen bonding and π-π interaction geometry in facilitating self-assembly of Fmoc-Phe-Phe.
能够自组装成具有水凝胶特性的纤维网络的低分子量试剂是很有前景的生物材料。由于对自组装机制、自组装材料的堆积结构以及自组装过程如何对应于水凝胶化的出现缺乏完善的理解，大多数低分子量水凝胶剂是通过经验或偶然发现的。在此，通过与将苯丙氨酸残基替换为相应的N-苄基甘氨酸类肽（Nphe）类似物的衍生物进行系统比较，探究了一种经过充分研究的低分子量水凝胶剂N-芴甲氧羰基二苯基丙氨酸（Fmoc-PhePhe）的自组装和水凝胶化机制。类肽是一种肽模拟物，它将侧链官能团的展示从α-碳转移到末端氮。在肽聚合物的背景下，这改变了类肽相对于相应氨基酸的氢键能力、侧链呈现几何形状、酰胺顺/反异构化平衡以及β-折叠潜力。研究发现，氨基酸/类肽杂化物Fmoc-Phe-Nphe和Fmoc-Nphe-Phe相对于母体二肽改变了纤维自组装倾向并降低了水凝胶化能力，并且二肽类Fmoc-Nphe-Nphe的纤维自组装完全受到抑制。这些发现为低分子量类肽和肽/类肽杂化物作为水凝胶化剂的潜力提供了见解，并阐明了氢键和π-π相互作用几何形状在促进Fmoc-Phe-Phe自组装中的重要性。
