CE11 - Caractérisation des structures et relations structure-fonctions des macromolécules biologiques

Fingerprinting of Glycosaminoglycans by Single Molecule Nanopore Sensing: Towards a sequencing tool for Glycosaminoglycomics – GAGS-NANOSENSOR

Submission summary

The project aims at providing the first analytical method at the single molecule level for the sequencing of bioactive glycosaminoglycan polysaccharides by using the nanopore sensing, with immediate applicability in biological and pathophysiological research, especially for diagnostic and identification of carbohydrate biomarkers. Given the central biological roles of GAGs and the growing focus on being promising pharmacological targets, a strong demand is rising for methods able to read GAGs oligosaccharide sequences, especially those that are specifically involved in pathological situations. Nanopore-based methods are thus promising for deciphering information encoded in a linear polymer, yet single molecule nanopore analysis remains however comparatively much less applied to carbohydrates, especially to the bioactive polysaccharide GAGs. Our goal in the GAGs-nanosensor project is to open up this as yet unexplored field of nanopore applied to GAGs, and for the first time to set-up a nanopore-based profiling and sequencing method for these bioactive carbohydrates. For that purpose, different protein nanopores will be evaluated, and unique libraries of synthetic and bio-engineered sulfated GAGs oligosaccharides designed as standard molecules will be produced to cover the widest molecular diversity found in GAGs. A database of reference nanopore signatures will be established through the nanopore screening of these GAGs libraries. The lack of carbohydrate-oriented structural tools is identified by international sciences foundations and academies as a critical bottleneck in the full development of glycosciences. Such nanopore sequencing method meet this demand and it will enhance the establishment of structure-activity relationship and the design of well-defined GAGs-based compounds as pharmacological tools and potential therapeutic agents.

Project coordinator

Monsieur Régis DANIEL (Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement)

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.

Partner

UPSaclay-ICMMO Université Paris Saclay-Institut de Chimie Moléculaire et des Matériaux d'Orsay
LAMBE Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement
ICOA Institut de Chimie Organique et Analytique
CERMAV CENTRE DE RECHERCHES SUR LES MACROMOLECULES VEGETALES

Help of the ANR 512,657 euros
Beginning and duration of the scientific project: October 2021 - 36 Months

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