Departament d'Enginyeria Química and Barcelona Research Center for Multiscale Science and Engineering, Universitat Politècnica de Catalunya, EEBE, C/Eduard Maristany, 10-14, Ed. I2, 08019 Barcelona, Spain.
Molecules. 2020 Dec 20;25(24):6037. doi: 10.3390/molecules25246037.
Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer's disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it was shown that the assembly preferences of this family of compounds is altered by capping both the - and C-termini using highly aromatic fluorenyl groups (i.e., fluorenyl-9-methoxycarbonyl and 9-fluorenylmethyl ester, named Fmoc and OFm, respectively). In this article the work performed in the field of the effect of the structure and incubation conditions on the morphology and polymorphism of short (from two to four amino acid residues) Phe-homopeptides is reviewed and accompanied by introducing some new results for completing the comparison. Special attention has been paid to the influence of solvent: co-solvent mixture used to solubilize the peptide, the peptide concentration and, in some cases, the temperature. More specifically, uncapped (FF, FFF, and FFFF), -capped with Fmoc (Fmoc-FF, Fmoc-FFF, and Fmoc-FFFF), C-capped with OFm (FF-OFm), and doubly capped (Fmoc-FF-OFm, Fmoc-FFF-OFm, and Fmoc-FFFF-OFm) Phe-homopeptides have been re-measured. Although many of the experienced assembly conditions have been only revisited as they were previously reported, other experimental conditions have been examined by the first time in this work. In any case, pooling the effect of highly aromatic blocking groups in a single study, using a wide variety of experimental conditions, allows a perspective of how the disappearance of head-to-tail electrostatic interactions and the gradual increase in the amount of π-π stacking interactions, affects the morphology of the assemblies. Future technological applications of Phe-homopeptides can be envisaged by choosing the most appropriate self-assemble structure, defining not only the length of the peptide but also the amount and the position of fluorenyl capping groups.
二苯丙氨酸肽（FF）自组装成刚性管状纳米结构，是阿尔茨海默病β-淀粉样蛋白（Aβ）多肽中非常短的核心识别基序。此外，已经证明苯丙氨酸（F 或 Phe）同肽能够自组装成有序的纳米结构。在这种情况下，已经表明，通过使用高度芳族芴基基团（即芴基-9-甲氧羰基和 9-芴基甲酯，分别命名为 Fmoc 和 OFm）封闭-N 端和 C 端，该化合物家族的组装偏好会发生变化。在本文中，综述了结构和孵育条件对短（两个到四个氨基酸残基）苯丙氨酸同肽形态和多态性的影响的研究工作，并引入了一些新的结果来完成比较。特别关注溶剂的影响：用于溶解肽的共溶剂混合物、肽浓度以及在某些情况下的温度。更具体地说，未封闭的（FF、FFF 和 FFFF）、用 Fmoc 封闭-N 端的（Fmoc-FF、Fmoc-FFF 和 Fmoc-FFFF）、用 OFm 封闭-C 端的（FF-OFm）和双重封闭的（Fmoc-FF-OFm、Fmoc-FFF-OFm 和 Fmoc-FFFF-OFm）苯丙氨酸同肽已重新测量。尽管许多经验性的组装条件仅作为先前报道的条件重新考察，但在这项工作中首次检查了其他实验条件。无论如何，在单个研究中汇集高度芳族封闭基团的影响，使用各种实验条件，可以了解头对头静电相互作用的消失和π-π堆积相互作用的逐渐增加如何影响组装体的形态。通过选择最合适的自组装结构，可以设想苯丙氨酸同肽的未来技术应用，不仅定义肽的长度，而且定义芴基封闭基团的数量和位置。
