Carbohydrate mimics for therapeutic applications: exploring their conformational preference in the gas and micro-hydrated phases. – CarboMim
Therapeutic sugars in the gas phase!
Carbohydrate mimics for therapeutic applications: exploring their conformational preference in the gas and micro-hydrated phases.<br />
Improve natural sugars to turn them into new drugs.
Glycotherapy aims at exploiting the properties of sugars by developing glycoconjugate and/or glycomimic molecules that have the carbohydrate capacity to reach their target (molecular recognition), while giving them a better therapeutic efficiency (stability at the active site, interaction with the target...). One of the challenges is to create systems with a robust enough conformational identity to be conserved accross the many diverse envorionments that a drug will encounter, from its synthesis until it reaches the therapeutic target in vivo.
Gas phase vibrational spectroscopy, very good probe of non-covalent interactions, and the exploration of the conformational landscapes by theoretical chemistry methods allow establishing the conformational preferences of such molecules, free of all interaction before studying how these preferences evolve upon micro-hydration, when a limited and controlled number of water molecules interact with the molecule.
We propose to study the conformational choices of isolated natural sugars (Lewis X and Lewis A) and the influence of few water molecules on these choices. Then we will study the conformation of glycomimics, synthesized by the Basel group for the development of new glycotherapy products.
The Basel group has innovated in synthetic strategies to produce large quantities of high purity samples that are necessary for the gas phase spectroscopy study that are perfomed in Orsay.
The first results obtained for the natural sugars Lewis A and Lewis X show that these two very similar glycans have very different conformational behaviors. Lewis A adopts a robust conformation that is unchanged upon single hydration, while Lewis X changes its conformation when it interacts with a single water molecule.
The study of Lewis A and Lewis X is now finished and we are going to start the second and central phase of the project by focusing on the conformation of the glycomimics. Several candidates ahve been synthesized by the Basel group and the spectroscopy experiments are in progress.
1. Spectroscopie IR/UV de carbohydrates neutres: glycoconjugués et glycomimiques isolés et hydratés.
PAMO-JSM SFP, mini-colloque « Enjeux et impact de la caractérisation structurelle de carbohydrates. », Bordeaux, 6/7/2016
2. Conformation de Glycomimiques isolés et hydratés en phase gazeuse.
Journée Scientifique de la Fédération de Chimie Physique Paris Saclay – 24/6/2016
3. Conformation of glycoconjugates and glycomimics in the gas phase.
Isolated Biomolecules and Biomolecular Interactions, Oxford, 10-15 Avril 2016.
Project coordination
Pierre Çarçabal (Institut des Sciences Molécoluaires d'Orsay)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partnership
ISMO Institut des Sciences Molécoluaires d'Orsay
UB Universität Basel
Help of the ANR 190,170 euros
Beginning and duration of the scientific project:
February 2014
- 36 Months
