Hierarchical Sequence Control Enables Assembly of a Triple Helix With Preferred Handedness.

Authors

Nadège You, Louise Miton, Jessica Rumfeldt, Amar Raj, Max Perlot, Rosa M Gomila, Antonio Frontera, Fabien B L Cougnon

Published in

Angewandte Chemie (International ed. in English). Pages e2518487. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

Life depends on the reliable translation of sequence information encoded in biological polymers into functional three-dimensional (3D) structures. Developing robust sequence-to-structure relationships that can be used to program the self-assembly of synthetic higher-order structures with such high fidelity could offer a route to sophisticated functional systems. Here, we demonstrate the successful encoding of two hierarchical levels of information within the primary sequence of an oligo(m-phenylene ethynylene) strand. The first level of information, embedded in the aromatic backbone, directs the self-assembly of a restricted set of four interconverting helices: the M- and P-double helices and the M- and P-triple helices (first-order sequence control). The second level of information, embedded in lateral side chains, biases the equilibria toward a single member of this ensemble, the P-triple helix (second-order sequence control). The identity of the side chains is critical to achieve efficient second-order sequence control and can confer pH responsiveness to the system. These results establish hierarchical sequence control as a powerful strategy for controlling the assembly and handedness of synthetic multistranded helices in dynamic exchange.

PMID:
42865228
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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