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Abstract Chiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates. We find that right-handed DNA triple helices well accommodate peptide triple coiled-coils of the same handedness, but not with the left-handed coiled-coil stereoisomers. This chiral communication is effective in a range (<4.5 nm) far beyond canonical IMF distance. Small-angle X-ray scattering and molecular dynamics simulation indicate that the interdomain linkers are tightly packed via hydrophobic interactions, which likely sustains the chirality transmission between DNA and peptide domains. Our findings establish that long-range chiral transmission occurs in tertiary macromolecular domains, explaining the presence of homochiral pairing of superhelices in proteins.
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This content will become publicly available on November 3, 2026
Mechanisms of Chiral Induction to Foldamer Backbones
Foldamers, oligomers that adopt well‐defined conformations, represent an efficient strategy toward nanoscale structural complexity. While most foldamers fold into helices, many abiotic foldamers are built from achiral repeat units and therefore do not have a preferred twist sense. Their handedness can, however, be controlled by attaching groups with chirality centers to the foldamer backbone. This process allows chiral information from readily available compounds to be amplified into larger‐scale structural asymmetry and translated into functional behavior. This review describes mechanisms whereby the point chirality of chiral “controller” groups directs foldamer twist sense. We highlight examples of aromatic oligoamides, oligohydrazides, oligoindoles, oligo(ortho‐phenylenes), oligooxymethylenes, and oligo(aminoisobutyric acids), examining cases where the controller groups are attached at either the helices’ termini or sides. Our emphasis is on applying intuitive concepts from conformational analysis and, where appropriate, computational modeling of small substructures. In each case, we consider first short‐range interactions that orient the controller group relative to its direct point of attachment to the foldamer, and then its long‐range interactions with more‐distant parts of the oligomer. Together, these interactions allow the twist sense to be predicted (or at least rationalized). Understanding these mechanisms should facilitate the design of systems with dynamic control over helicity.
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- Award ID(s):
- 2304670
- PAR ID:
- 10646119
- Publisher / Repository:
- Wiley-VCH GmbH
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 31
- Issue:
- 61
- ISSN:
- 0947-6539
- Page Range / eLocation ID:
- e02433
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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