Division of BioAnalytical Chemistry, AIMMS Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HV Amsterdam, The Netherlands.
Radboud University, FELIX Laboratory, Institute for Molecules and Materials, Toernooiveld 7, 6525 ED Nijmegen, The Netherlands.
Molecules. 2022 Apr 6;27(7):2367. doi: 10.3390/molecules27072367.
Peptide segments with phenylalanine residues are commonly found in proteins that are related to neurodegenerative diseases. However, the self-assembly of phenylalanine-based peptides can be also functional. Peptides containing phenylalanine residues with different side caps, composition, and chemical alteration can form different types of nanostructures that find many applications in technology and medicine. Various studies have been performed in order to explain the remarkable stability of the resulting nanostructures. Here, we study the early stages of self-assembly of two phenylalanine derived peptides in the gas phase using IR action spectroscopy. Our focus lies on the identification of the key intra- and intermolecular interactions that govern the formation of the dimers. The far-IR region allowed us to distinguish between structural families and to assign the 2-(2-amino-2-phenylacetamido)-2-phenylacetic acid (PhgPhg) dimer to a very symmetric structure with two intermolecular hydrogen bonds and its aromatic rings folded away from the backbone. By comparison with the phenylalanine-based peptide cyclic -phenylalanyl--phenylalanine (cyclo-FF), we found that the linear FF dimer likely adopts a less ordered structure. However, when one more phenylalanine residue is added (FFF), a more structurally organized dimer is formed with several intermolecular hydrogen bonds.
含苯丙氨酸残基的肽段通常存在于与神经退行性疾病相关的蛋白质中。然而，基于苯丙氨酸的肽的自组装也可能具有功能性。含有不同侧链帽、组成和化学修饰的苯丙氨酸残基的肽可以形成不同类型的纳米结构，这些结构在技术和医学中有许多应用。为了解释所得纳米结构的显著稳定性，已经进行了各种研究。在这里，我们使用红外作用光谱法研究了气相中两种由苯丙氨酸衍生的肽的自组装的早期阶段。我们的重点是确定控制二聚体形成的关键分子内和分子间相互作用。远红外区域使我们能够区分结构族，并将 2-(2-氨基-2-苯乙酰氨基)-2-苯乙酸（PhgPhg）二聚体分配给具有两个分子间氢键的非常对称的结构，其芳环从主链折叠。与基于苯丙氨酸的肽环状 -苯丙氨酰基--苯丙氨酸（cyclo-FF）相比，我们发现线性 FF 二聚体可能采用了不太有序的结构。然而，当再添加一个苯丙氨酸残基（FFF）时，会形成具有几个分子间氢键的更结构化的二聚体。
