Abstract :
[en] Foldamers are artificial folded molecular architectures inspired by the structures and functions of natural biopolymers. Folding is the process selected by nature to control the conformation of its molecular machinery to carry out chemical functions and mechanical tasks, such as en-zyme catalysis, duplication in nucleic acids, force generation,...
During the last decade of research on foldamers [1], synthetic oligomers able to adopt well-defined and predictable folded conformations, such as helices, have been proposed. Recent progress has shown that stepwise chemical synthesis and molecular design based on aromatic oligoamide backbones enable to produce large helically folded molecular architectures. The shape and stiffness of the backbone, local conformational preferences, specific interactions between distant monomers in sequences, as well as the action of external parameters such as the solvent or the presence of ions, can be combine to induce folding tendency. A remarkable aspect of these architectures is that they can give rise to folded patterns that have no in natural counterparts biopolymer structures. For instance, helices whose diameter varies along the se-quence, helices possessing a handedness inversion centre, herringbone helices have been reported.
The objective of the project is to synthesize various helical nanorchitectures based on an oli-goamide aromatic backbone and to obtain a detailed picture of their dynamical conformation in solution, as well as, their mechanochemical properties, by AFM-based single molecule force spectroscopy. It is worth mentioning that an important sub-objective of this project is to probe intramolecular interactions in small synthetic molecules with the AFM. Indeed, whereas single-molecule force spectroscopy on macromolecules (proteins and synthetic polymers) is widely exploited[2], implementing single-molecule force spectroscopy on small molecules, such as the foldamers proposed here, remains a major challenge[3].
[1] For a review, see G. Guichard and I. Huc, Chem. Commun. 2011, 47, 5933–5941.
[2]E. M. Puchner, H. E.Gaub, Curr. Opin. Struct. Biol. 2009, 19, 605–614.
[3]P. Lussis, A.-S. Duwez, Nature Nanotech. 2011, 6, 553-557
