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 enzyme catalysis, information storage, duplication in nucleic acids, force generation,… 

Since the twists and folds of biomolecules explicitly underpin their form and function, the task of imparting synthetic molecules and macromolecules with folded secondary structures should have enormous potential to yield functional materials with novel and emergent properties. Accordingly, the synthesis of artificial molecules that adopt folded secondary structures represent a very rich and active field of research.[1] 

Simple long sequences consisting of a constant regular repeat motif have entered a regime of routine engineering. Besides those classical structures, original and much more complex structures like branched aromatic-aliphatic hybrid oligoamide foldamers have been synthesized very recently.[2,3] However, a detailed picture of the properties of these systems is still missing. Ensemble techniques here show their limitation. There is still a lack of detailed and quantitative information on the basic forces and (multiple) cooperative processes that govern the folding. 

Much of the exquisite and detailed information about how natural biomolecules fold and operate has been gleaned from direct measurements made on single molecules with optical tweezers or force clamp atomic force microscopy (AFM).[4,5] Along the same lines, we propose here to study oligoamide foldamers by AFM-based single molecule force spectroscopy to gain detailed insight into the forces governing the folding and mechanochemical properties. The possibility of generating force during the refolding process will be evaluated, paving the way to the use of these systems as nanomachines. 

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,[6] implementing single-molecule force spectroscopy on small molecules, such as the foldamers proposed here, remains a major challenge.[7]


[1] For a review, see G. Guichard and I. Huc, Chem. Commun. 2011, 47, 5933–5941.
[2] D. Sanchez-Garcia, ?B. Kauffmann, T. Kawanami, H. Ihara, M. Takafuji, M.-H Delville, I. Huc, J. Am. Chem. Soc. 2009, 131, 8642–8648.
[3]N. Delsuc, S. Massip, J.-M. Léger, B. Kauffmann, I. Huc, J. Am. Chem. Soc. 2011, 133, 3165–3172.
[4]C.Bustamante, Y. R. Chemla, N. R Forde, D. Izhaky, Annu. Rev. Biochem. 2004, 73, 705-748.
[5]Special issue. Annu. Rev. Biochem. 2008, 77, 45-228
[6]E. M. Puchner, H. E.Gaub, Curr. Opin. Struct. Biol. 2009, 19, 605–614.
[7]P. Lussis, T. Svaldo-Lanero, A. Bertocco, C.-A. Fustin, D. A. Leigh, A.-S. Duwez, Nature Nanotech. 2011, 6, 553-557

Project partners and their Roles

Nanochem-Department of Chemistry, University of Liège

Atomic force microscopy, surface characterization, single-molecule force spectroscopy

Institut Européen de Chimie et Biologie, University of Bordeaux
Foldamers synthesis

PROFACTOR ( — Steyr-Gleink, Austria): development of materials and surfaces based on nanotechnology and micro- and nanostructuring