Remote Conformational Control of a Chloride‐Binding Site

Peptide foldamers, each with a stereogenic C‐terminal bis(squaramide) separated from an N‐terminal amino acid “controller” by an α‐aminoisobutyric acid (Aib) tetramer, have been shown to bind chloride. Chloride affinity is sensitive to the sense and strength of screw‐sense induction by each N‐terminal residue, a conformational preference that is relayed along the 1‐nanometer‐long helical foldamer. Chloride binding is weaker when the screw‐sense preference of the chiral N‐terminal residue matches that of the C‐terminal binding site, whereas mismatches in screw‐sense preferences give stronger chloride binding. X‐ray crystallography and computational modeling provide a simple model for this relationship between chloride affinity and the screw‐sense preferences of both terminal groups. Chloride binding allows these foldamers to act as ion carriers in the bulk phase, but in bilayers, the length of each foldamer is more important for activity. The use of a helical relay to remotely control the binding of an achiral anion may offer pathways toward the remote allosteric control of chloride binding by macromolecules.

• Publication year

  2025

• Venue

  ChemistryEurope

• Publication date

  2025-09-18

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1002/ceur.202500195
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Reaction, Recognition, Relay: Anhydride Hydrolysis Reported by Conformationally Responsive Fluorinated Foldamers in Micelles.

  2024cited by this paper
• Foldamer-mediated transport across phospholipid bilayers.

  2024cited by this paper
• Innovative Self‐Assembly of 15‐Mer Chimeric α‐Peptide–Oligourea Foldamers toward Cl−‐Selective Ion Channels

  2024cited by this paper
• Anion‐Dependent Hydrogen‐Bond Polarity Switching in Ethylene‐bridged Urea Oligomers

  2023cited by this paper
• Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes

  2023cited by this paper
• Chemically Fueled Communication Along a Scaffolded Nanoscale Array of Squaramides

  2023cited by this paper
• Light-Driven Photoconversion of Squaramides with Implications in Anion Transport

  2023cited by this paper
• Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer

  2023cited by this paper
• Formation of supramolecular channels by reversible unwinding-rewinding of bis(indole) double helix via ion coordination

  2022cited by this paper
• Reversible Capture and Release of a Ligand Mediated by a Long-Range Relayed Polarity Switch in a Urea Oligomer

  2022cited by this paper
• Revealing the Hidden Costs of Organization in Host-Guest Chemistry Using Chloride-Binding Foldamers and Their Solvent Dependence.

  2022cited by this paper
• α‐Amino‐iso‐Butyric Acid Foldamers Terminated with Rhodium(I) N‐Heterocyclic Carbene Catalysts

  2021cited by this paper
• Polarity-Tolerant Chloride Binding in Foldamer Capsules by Programmed Solvent-Exclusion.

  2021cited by this paper
• Self-Assembly of Size-Controlled m-Pyridine-Urea Oligomers and Their Biomimetic Chloride Ion Channels.

  2021cited by this paper
• Photomodulation of Transmembrane Transport and Potential by Stiff-Stilbene Based Bis(thio)ureas

  2021cited by this paper
• Artificial transmembrane ion transporters as potential therapeutics

  2021cited by this paper
• Molecular Recognition by Zn(II)‐Capped Dynamic Foldamers

  2020cited by this paper
• Transmembrane Ion Channels Formed by a Star of David [2]Catenane and a Molecular Pentafoil Knot

  2020cited by this paper
• Oligo(5-amino-N-acylanthranilic acids): Amide Bond Formation without Coupling Reagent and Folding upon Binding Anions.

  2020cited by this paper
• Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors.

  2019cited by this paper
• The Versatility of Squaramides: From Supramolecular Chemistry to Chemical Biology

  2019cited by this paper
• Oligoamide Foldamers as Helical Chloride Receptors-the Influence of Electron-Withdrawing Substituents on Anion-Binding Interactions.

  2019cited by this paper
• Chloride ions stabilize the glutamate‐induced active state of the metabotropic glutamate receptor 3

  2018cited by this paper
• Sequence-Controlled Stimuli-Responsive Single-Double Helix Conversion between 1:1 and 2:2 Chloride-Foldamer Complexes.

  2018cited by this paper
• GFN2-xTB-An Accurate and Broadly Parametrized Self-Consistent Tight-Binding Quantum Chemical Method with Multipole Electrostatics and Density-Dependent Dispersion Contributions.

  2018cited by this paper
• Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor

  2017cited by this paper
• High-Affinity Anion Binding by Steroidal Squaramide Receptors

  2015cited by this paper
• Length-Dependent Formation of Transmembrane Pores by 310-Helical α-Aminoisobutyric Acid Foldamers

  2015cited by this paper
• Engineering the structure of an N-terminal β-turn to maximize screw-sense preference in achiral helical peptide chains.

  2014cited by this paper
• Foldamer-mediated remote stereocontrol: >1,60 asymmetric induction.

  2014cited by this paper
• Sulfate-selective recognition by using neutral dipeptide anion receptors in aqueous solution.

  2014cited by this paper
• Left-handed helical preference in an achiral peptide chain is induced by an L-amino acid in an N-terminal type II β-turn.

  2013cited by this paper
• A new family of bioorthogonally applicable fluorogenic labels.

  2013cited by this paper
• End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching

  2013cited by this paper
• Anion-driven reversible switching of metal-centered stereoisomers in metallopeptides.

  2013cited by this paper
• Induction of unexpected left-handed helicity by an N-terminal L-amino acid in an otherwise achiral peptide chain.

  2012cited by this paper
• Squaramides as potent transmembrane anion transporters.

  2012cited by this paper
• Squaramides: physical properties, synthesis and applications.

  2011cited by this paper
• Densities and Viscosities of Binary and Ternary Mixtures of (Nitrobenzene + 1-Bromobutane), (1-Bromobutane + Methylcyclohexane), (Nitrobenzene + Methylcyclohexane), and (Methylcyclohexane + Nitrobenzene + 1-Bromobutane) from (293.15 to 308.15) K

  2011cited by this paper
• Synthetic foldamers.

  2011cited by this paper
• Squaramides: bridging from molecular recognition to bifunctional organocatalysis.

  2011cited by this paper
• Structure–Activity Relationships in Tripodal Transmembrane Anion Transporters: The Effect of Fluorination

  2011cited by this paper
• N-versus C-terminal control over the screw-sense preference of the configurationally achiral, conformationally helical peptide motif Aib(8)GlyAib(8).

  2010cited by this paper
• Squaramide-catalyzed enantioselective Michael addition of diphenyl phosphite to nitroalkenes.

  2010cited by this paper
• Highly enantioselective Michael addition of nitroalkanes to chalcones using chiral squaramides as hydrogen bonding organocatalysts.

  2010cited by this paper
• Transfer of noncovalent chiral information along an optically inactive helical peptide chain: allosteric control of asymmetry of the C-terminal site by external molecule that binds to the N-terminal site.

  2009cited by this paper
• Quantifying end-to-end conformational communication of chirality through an achiral peptide chain.

  2009cited by this paper
• Stereospecific synthesis of C2 symmetric diamines from the mother diamine by resonance-assisted hydrogen-bond directed diaza-Cope rearrangement.

  2008cited by this paper
• X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity

  2002cited by this paper
• Noncovalent domino effect on helical screw sense of chiral peptides possessing C-terminal chiral residue.

  2002cited by this paper
• Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: structure of the enzyme with chloride bound.

  2000cited by this paper
• Linear oligopeptides. Part 406. 1 Helical screw sense of peptide molecules: the pentapeptide system (Aib) 4 / L -Val[ L -(αMe)Val] in solution

  1998cited by this paper
• Program DYNAFIT for the analysis of enzyme kinetic data: application to HIV proteinase.

  1996cited by this paper
• The chloride effect in human haemoglobin. A new kind of allosteric mechanism.

  1994cited by this paper
• Long-wavelength chloride-sensitive fluorescent indicators.

  1994cited by this paper
• Excess molar volumes and excess viscosities of 2-propanol + methylacetate + dichloromethane system at 298.15 K

  1988cited by this paper
• Conformational Transitions between Enantiomeric 310‐Helices

  1987cited by this paper
• the original work is properly cited.

  year unknowncited by this paper

• No citing papers are available for this paper.