Bioorthogonal chemical glycobiology

Research

The Fascione group studies carbohydrates at the interface between chemistry and biology- a field commonly termed ‘chemical glycobiology’. Our focus is on deciphering the roles that carbohydrates play in the etiology of disease and applying this knowledge in the development of innovative new therapeutics. To achieve this goal we develop new methods for bioorthogonal chemistry and protein bioconjugation, using small molecule organocatalysts and an interdisciplinary toolkit of techniques including synthetic and automated carbohydrate chemistry, solid phase peptide synthesis (SPPS), the enzymatic and chemical modification of proteins, unnatural amino acid mutagenesis and molecular enzymology.

 

Automated oligosaccharide synthesis

The biochemistry and cell biology of oligo- and polysaccharides (the “Glyco-code”) still remains one of the least understood areas in bioscience. This is primarily a result of the limited availability of  biologically relevant pure glycopolymers. The MAF lab is home to the UK's first automated oligosaccharide synthesiser, the Glyconeer, which we employ in the rapid solid phase synthesis of complex biologically relevant oligo/polysaccharides, and glycopeptides.

The Glyconeer was installed in York in 2015, and is a collaborative UK venture purchased with funds awarded by a BBSRC ALERT 14 grant, and the University of York. We are committed to training and working collaboratively with glycoscientists across the UK, so please contact MAF if you have a project and would like to use and train on the Glyconeer.

 

research1

Bioorthogonal protein chemistry

New strategies for the bioorthogonal modification of proteins are revolutionising the fields of chemical medicine, chemical biology, and cell biology. By exploiting ‘chemical handles’ which can be tagged in bioconjugation reactions, scientists have been able to probe, perturb, and visualise dynamic cellular processes in vitro, ex vivo, and even inside whole living organisms. In the MAF lab we are pioneering new methods for the chemical modification of proteins that generate stable C-C bonds under biologically relevant conditions and also allow multi-functionalisation. We utilise our expertise in chemical glycobiology in combination with a range of interdisciplinary methods including chemical synthesis, organocatalysis, protein chemistry, unnatural amino acid mutagenesis and molecular biology to showcase the utility of these new bioconjugation reactions in collaborative ‘real world’ chemical biology studies and in the development of novel biomedical protein conjugates and ‘glycotherapeutics’.

Chemical and molecular enzymology for glycobiology

In the MAF lab we are developing new methods for unnatural amino acid mutagenesis which we employ in 'chemical enzymology' studies with the aim of exploring mechanisms in carbohydrate active enzymes (CAZymes), and the biological roles of carbohydrate in the ethology of disease. We have a particular interest in the processing and biosynthesis of rare sugars in emerging multi drug resistant bacteria.

research2
Research3

Synthetic and mechanistic carbohydrate chemistry

We also have an ongoing interest in stereoselective glycosylation reactions and develop new methods for the synthesis of anomerically pure oligo- and polysaccharides, and explore the mechanisms of these reactions using synthetic carbohydrate chemistry methods as our primary tool.

Research4

Current active projects

Organocatalysis for the bioorthogonal modification of proteins

The chemical glycobiology and processing of rare sugars in multidrug resistant bacteria

The automated synthesis of biologically relevant oligo- and polysaccharides

Bioorthogonal modification of unnatural amino acids for homogenous N-glycoprotein synthesis

Directed evolution of biocatalysts for metabolic oligosaccharide engineering

Bitnami