Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose

Nagula Chandramouli (1) , Yann Ferrand (1) , Guillaume Lautrette (1) , Brice Kauffmann (1) , Cameron David Mackereth (1) , Michel Laguerre (1) , Didier Dubreuil (2) , Ivan Huc (1)

1 CBMN - Chimie et Biologie des Membranes et des Nanoobjets
2 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation

The ab initio design of synthetic molecular receptors for a given biomolecular guest remains an elusive objective. We describe a powerful and novel approach to produce receptors of exquisite selectivity in the challenging context of monosaccharide recognition by using an iterative evolution process that exploits the modular structure of folded synthetic oligomer sequences coupled with molecular modelling and structural characterisation. Starting from a first principles design taking size, shape and hydrogen-bonding ability into account, and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallise, a sequence that binds to -D-fructopyranose in organic solvents with atomic scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol by which to create selective receptors towards an eventual wide range of monosaccharides or other biological and synthetic compounds.

Domaines: Chimie

Nagula Chandramouli, Yann Ferrand, Guillaume Lautrette, Brice Kauffmann, Cameron David Mackereth, et al.. Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose. Nature Chemistry, 2015, 7 (4), pp.334-341. ⟨10.1038/nchem.2195⟩. ⟨hal-01509470⟩