Research Interests:

The Flitsch group is very interdisciplinary, consisting of synthetic chemists, enzymologists and molecular biologists and is involved in several topics that fall within the broad area of Chemical Biology. We enjoy collaboration with UK and international groups and are involved in a number of large multidisciplinary and international projects: “Glycoarrays” (SLF coordinator) involve seven UK groups concerned with the development of carbohydrate arrays; “EuroGlycoArrays” is an EC funded project involving 14 groups from all over Europe; “Combiocat” is an European consortium including groups from Italy, Germany, UK and Sweden concerned with Biocatalysis on solid phase. We are also part of a COST-D31 network on combinatorial dynamic chemistry. Our research interests fall into three broad areas:

Glycosciences – More than half of the proteins in the body are glycosylated, but the role of sugars attached to proteins is very poorly understood. We are using a combination of chemical synthesis, protein chemistry, molecular biology and biophysical methods to understand the effect glycosylation has on protein structure, folding and function. Key to the success of these studies are novel tools that we have developed for the synthesis of defined glycoproteins which are not available from natural sources. Such tools can be used in practical applications to stabilize protein structure and improve protein function.

Biocatalysis – Enzymes have enormous potential as catalysts for the production of fine chemicals, pharmaceuticals, agrochemicals and health care products. They can catalyse reactions with high regio- and stereoselectivity under ambient reaction conditions. We are interested in expanding the repertoire of biocatalytic reactions by developing novel biocatalysts for reactions that are chemically very difficult. Of particular interest are two classes of enzymes:

Monooxygenases – enzymes that can use molecular oxygen for the selective oxidation of a broad range of organic compounds, even the hydroxylation of nonfunctionalised hydrocarbons. Glycosyltransferases catalyse the regio- and stereoselective formation of glycosidic bonds in saccharides and have been shown to be important tools for the rapid synthesis of biologically active carbohydrates and glycoconjugates.

Most recently, we have started to use biocatalysts on substrates attached to the solid phase, which are of interest in high-throughput chemical synthesis and biological analysis.

Protein-Ligand Interactions – The de-novo design of selective ligands (substrates, inhibitors, agonists or antagonists) of target protein is still a very challenging proposition. We are using a combination of virtual screening of compound libraries in combination with experimental library screening to find novel protein ligands. An ongoing project is concerned with the design and synthesis of novel blockers of Aquaporins, ubiquitous water channels common to many tissues and organs in our body. Water transport through membranes is key many important physiological functions and Aquaporins are important targets for therapeutic intervention.