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Aromatic stacking in Glycochemistry: can glycosidations be tamed?

Project description

How sweet it is: Achieving better control over glycosidation reactions

Glycans, also known as carbohydrates, saccharides or sugars, are ubiquitous in cells and play critical roles in cellular processes. They are polymers made up of different combinations of monomers or monosaccharides that form complex 3D structures. These glycans are also often linked to other non-sugar molecules. One of the important ways this is achieved is through glycosidation or the formation of glycosidic bonds. Given the critical role of glycans in important application domains, including biomedicine, energy and biotechnology, the EU-funded SWEET-PI project will investigate routes to better synthetic control over the multiple steps and species involved in glycosidation reactions.

Objective

Progress in chemical synthesis has provided access to a large variety of complex glycostructures, having a major impact in the expansion of Glycoscience. Central to carbohydrate chemistry is the glycosidation reaction, which involves the formation of a glycosidic bond between donor and acceptor molecules. It is commonly accepted that this process requires the formation of transient ionic species, whose stability, conformational properties and interactions determine to a large extend the reaction outcome. In principle, these elusive species are stabilized by means of inter- and intramolecular interactions, and in fact, this is a key feature for the activity of glycosidases and glycosyltransferases, typically requiring the participation of electron-rich functional groups, such as carboxylates. Interestingly, aromatic/carbohydrate interactions have too been detected and evaluated as supramolecular recognition motifs but, to the best of our knowledge, never at the reaction intermediate level, despite being frequently invoked to play a major role during enzymatic catalysis. Our hypothesis in this project revolves around the idea that stacking interactions involving electron-rich aromatic systems can be employed to stabilize the glycosyl oxocarbenium ion and to enhance the glycosyl acceptor reactivity; in the first case, these contacts might increase the life-time of the cationic intermediates, facilitating their detection and potentially allowing the modulation of the glycosidic donor in order to better control the stereochemical course of the reaction. Alternatively, CH/pi complexes involving the glycosyl acceptor could enhance the electron density of the reactive functional group, thus its nucleophilicity. This project aims to test both aspects of the carbohydrate/aromatic interaction employing a bioorganic approach based on the design, synthesis and systematic analysis of appropriate molecular models.

Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 172 932,48
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost
€ 172 932,48