Morphology Transformation of Foldamer Assemblies Triggered by Single Oxygen Atom on Critical Residue Switch

Abstract

The synthesis of morphologically well‐defined peptidic materials via self‐assembly is challenging but demanding for biocompatible functional materials. Moreover, switching morphology from a given shape to other predictable forms by molecular modification of the identical building block is an even more complicated subject because the self‐assembly of flexible peptides is prone to diverge upon subtle structural change. To accomplish controllable morphology transformation, systematic self‐assembly studies are performed using congener short β‐peptide foldamers to find a minimal structural change that alters the self‐assembled morphology. Introduction of oxygen‐containing β‐amino acid (ATFC) for subtle electronic perturbation on hydrophobic foldamer induces a previously inaccessible solid‐state conformational split to generate the most susceptible modification site for morphology transformation of the foldamer assemblies. The site‐dependent morphological switching power of ATFC is further demonstrated by dual substitution experiments and proven by crystallographic analyses. Stepwise morphology transformation is shown by modifying an identical foldamer scaffold. This study will guide in designing peptidic molecules from scratch to create complex and biofunctional assemblies with nonspherical shapes.

Conformational landscapes of artificial peptides predicted by various force fields: are we ready to simulate β-amino acids?

“…Because there were six residues for each peptide, five inter-residue angles could be determined; denotes the average of five angles. For the triad structure obtained from the experiment, 3 the value was expected to be approximately 120° (Fig. 2C), in contrast to the typical pentad repeat whose ∼ 144° (Fig.…”

“…2B). 3 We introduced a geometric parameter to quantitatively analyze the structure of each local minimum from the hexamer simulations. First, we calculated the principal axis of the foldamer helix structure and projected the structure through this axis.…”

“…Chemists have long sought to demonstrate whether it is possible to chemically expand the set of building blocks beyond canonical amino acids by changing the backbone 1 and/or the side chain moiety. 2,3 Artificial oligopeptides that tend to fold into specific shapes are called foldamers. 4,5 They can show unique preferences in secondary structures 6–9 and sophisticated assembled structures.…”

Optimized stereoselective and scalable synthesis of five‐membered cyclic trans‐β‐amino acid building blocks via reductive amination

“…On the other hand, the reductive amination approach, involving a β-keto ester and chiral amine in the presence of AcOH and NaBH 3 CN, typically produces transdiastereomers. These intermediates lead to valuable compounds such as 2-aminocyclopentanecarboxylic acid (ACPC), 20 4-aminopyrrolidine-3-carboxylic acid (APC), 21 4-aminotetrahydrofuran-3-carboxylic acid (ATFC), 22 and 4-aminotetrahydrothiophene-3-carboxylic acid (ATTC). 23 While stereocontrolled routes to craft these alicyclic and heterocyclic β-amino acid derivatives are well documented, achieving satisfactory isolated yields, especially for trans-diastereomers, remains challenging.…”

Unraveling Molecular Assembly and Tracking Lipid Droplets Dynamics using Fluorescent Phenanthroimidazole Derivatives

“…3,[10][11][12][13][14][15][16][17][18] A range of materials has been developed through the tiny change in molecular structures like single atom alteration, side-chain modifications, etc. [19][20][21][22][23][24] However, the fundamental understanding of the dynamics of self-assembly to tune the task-specific functions of molecular materials remains a challenge. The molecular assembly process has a great impact on the size and shape of the aggregate structures and can be tuned through the variation of the local environments like polarity, the viscosity of the medium, and external stimuli like pH, temperature, and light.…”