A breakthrough in the design of synthetic sugar receptors

Two IECB teams, in collaboration with a research team of the University of Nantes, have just developed a method to design selective sugar receptors, a breakthrough just released in the prestigious journal Nature Chemistry.

Research results reported by the groups of Drs. Ivan Huc and Cameron Mackereth on synthesizing a foldamer able to selectively encapsulate fructose have indeed just been published online, 16 March 2015. This result is the first of its kind!

Sugars such as glucose, fructose, mannose or galactose exist in different forms and are particularly difficult to discriminate. The high selectivity of a specific foldamer towards fructose thus seems to be a promising solution regarding such an issue.

Designed from modular artificial strands and able to fold into well-defined conformations, foldamers may form cavities complementary to small molecules such as monosaccharides. The highly predictable structure of these artificial molecules is a clear advantage in creating new receptors.

In collaboration with Cameron Mackereth from the IECB and Didier Dubreuil from the University of Nantes, Ivan Huc*, a foldamer specialist at the Institute, and his team have successfully developed an efficient synthetic route to tailor these new molecules:

A first-generation foldamer was first produced from first principles by simply considering the size and properties of the cavity formed by the helically folded oligomer. Next, through the elucidation of the interactions between this foldamer and fructose, our researchers adopted a structure-based iterative approach to progressively modify the sequence of the strands so as to end-up with the desired cavity. In only a few iterations they obtained a new host-guest complex with unprecedented selectivity.

Beyond fructose, this novel and original approach could pave the way to a general strategy aiming at discriminating resembling sugars and also other important molecules.

As a continuation of this work, one may envisage that such host-guest molecules could lead to a new family of molecular probes to discriminate and titrate sugars in biological media.

A new generation of selective receptors to monitor closely!

Download the publication

Reference: Nagula Chandramouli, Yann Ferrand, Guillaume Lautrette, Brice Kauffmann, Cameron D. Mackereth, Michel Laguerre, Didier Dubreuil, Ivan Huc

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

Nature Chemistry – electronic release on March, 16th, 2015

*: The team is part of the unit CBMN (UMR 5248 – CBMN)