Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation

• Published in: Nature chemistry 2015-11, Vol.7 (11), p.871-878
• Main Authors: Collie, Gavin W., Pulka-Ziach, Karolina, Lombardo, Caterina M., Fremaux, Juliette, Rosu, Frédéric, Decossas, Marion, Mauran, Laura, Lambert, Olivier, Gabelica, Valérie, Mackereth, Cameron D., Guichard, Gilles
• Format: Article
• Language: English
• Subjects: 140/131; 140/137; 140/58; 639/638/541/966; 639/638/92/552; 639/638/92/611; 639/925/357/537; Analytical Chemistry; Biochemistry; Biomaterials; Biomimetics; Biopolymers; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Crystallography, X-Ray; Design; Inorganic Chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Nanostructures; Organic Chemistry; Peptides; Peptides - chemistry; Physical Chemistry; Polymers - chemistry; Urea - chemistry
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.2353

The design and construction of biomimetic self-assembling systems is a challenging yet potentially highly rewarding endeavour that contributes to the development of new biomaterials, catalysts, drug-delivery systems and tools for the manipulation of biological processes. Significant progress has been achieved by engineering self-assembling DNA-, protein- and peptide-based building units. However, the design of entirely new, completely non-natural folded architectures that resemble biopolymers (‘foldamers’) and have the ability to self-assemble into atomically precise nanostructures in aqueous conditions has proved exceptionally challenging. Here we report the modular design, formation and structural elucidation at the atomic level of a series of diverse quaternary arrangements formed by the self-assembly of short amphiphilic α-helicomimetic foldamers that bear proteinaceous side chains. We show that the final quaternary assembly can be controlled at the sequence level, which permits the programmed formation of either discrete helical bundles that contain isolated cavities or pH-responsive water-filled channels with controllable pore diameters. The self-assembly of short amphiphilic α-helicomimetic foldamers bearing proteinaceous side-chains can be controlled by manipulating the side-chain sequence. This enables the foldamers to be programmed to form either discrete helical bundles containing isolated cavities, or pH-responsive water-filled channels with controllable pore diameters.