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Constructing artificial ion channels is a challenging task. Herein, the de novo design of transmembrane ion channels made up of amphiphilic peptide–oligourea chimeric helices is described. They consist of an oligourea segment (7‐mer) attached to the C‐terminus of a short peptide (8‐mer). Mass spectrometry (MS) and transmission electron microscopy (TEM) analyses show that in an aqueous solution, two of these chimeras (HPU‐E and HPU‐N) independently form defined oligomeric structures. TEM also shows that they form fiber bundles. The third related chimera HPU‐F does not oligomerize (MS) but forms spherical nanostructures (TEM). HPU‐E and HPU‐N exhibit anion transport activity across lipid bilayers via antiport mechanism (HPU‐N > HPU‐E). The anion selectivity of HPU‐N is Cl−>NO3− > Br−>SCN− > I− > AcO−>F−, which can be due to anion binding within the channels rather than size exclusion. Patch‐clamp data support HPU‐N's Cl− selectivity (PCl−/PI− = 3.26). X‐ray crystal structure (1.77 Å) of HPU‐N reveals well‐packed α‐helices, and cryo‐electron microscopy data shows the formation of nanotubes (13.7 Å diameter pores) and transmembrane channels. The study shows that α‐peptide–oligourea‐based de novo design can yield unique bioactive molecules with defined structures and functions. [ABSTRACT FROM AUTHOR]

We introduce a novel cyclic β‐amino acid, trans‐(3S,4R)‐4‐aminotetrahydrothiophene‐3‐carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of β‐peptide hexamers containing ATTC using various techniques, including X‐ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC‐containing foldamers can adopt 12‐helical conformations similar to their isosteres and offer the possibility of fine‐tuning their properties via post‐synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post‐synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic β‐amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond. [ABSTRACT FROM AUTHOR]

Coordination polymers from α‐amino acids are promising organic–inorganic hybrid composites with chirality and biocompatibility. However, coordination polymers from unnatural amino acids are rarely studied. Here, we report the transition metal complexes from an unnatural β‐amino acid, (1S,2S)‐2‐aminocyclopentanecarboxylic acid, affording two possible coordination modes from the conformationally rigid cyclopentane ring. X‐ray crystallographic analysis revealed that Zn(II) formed a two‐dimensional (2D) coordination polymer via N,O‐bridging mode. In contrast, Cu(II) formed a discrete complex via N,O‐chelating mode and then constructed a 2D supramolecular network stabilized by hydrogen bonding between water and the ligands. [ABSTRACT FROM AUTHOR]

There is considerable interest in the rational design of controllable, bioinspired supramolecular systems as a potential means to create new biocompatible and functional materials able to mimic and build upon the characteristics of natural biopolymers. Here, the alcohol‐controlled aqueous self‐assembly of an amphiphilic helical oligourea foldamer (artificial folded oligomer) into a diverse array of tubular fibril architectures is reported. Electron microscopy studies provide details of the morphological evolution of the foldamer nanostructures from protofibrils to fibers, with high resolution X‐ray crystal structures providing an atomic‐scale view of these assemblies, and solution studies indicating the assembly and morphology to be affected by alcohol polarity and concentration. Overall, the results reported here highlight oligourea foldamers as suitable building blocks for the formation of a diverse range of tubular morphologies in a controllable manner. [ABSTRACT FROM AUTHOR]

Amino acids, foldamers, peptidomimetics, post-synthetic modification Keywords: amino acids; foldamers; peptidomimetics; post-synthetic modification EN amino acids foldamers peptidomimetics post-synthetic modification 1 1 1 09/20/23 20230925 NES 230925 B Post-synthetic modifications b of helical -peptide are achieved by a novel thioether-containing -amino acid, I trans i -(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC). Foldamers containing ATTC maintain their 12-helical conformation while offering versatile chemical transformations such as desulfurization, tagging, oxidation, and dimerization. [Extracted from the article]

Keywords: amino acids; foldamers; peptidomimetics; post-synthetic modification EN amino acids foldamers peptidomimetics post-synthetic modification 1 1 1 09/20/23 20230925 NES 230925 B Post-synthetic modifications b of helical -peptide are achieved by a novel thioether-containing -amino acid, I trans i -(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC). Foldamers containing ATTC maintain their 12-helical conformation while offering versatile chemical transformations such as desulfurization, tagging, oxidation, and dimerization. Inside Cover: Versatile Post-synthetic Modifications of Helical -Peptide Foldamers Derived from a Thioether-Containing Cyclic -Amino Acid (Angew. [Extracted from the article]