Final Report Summary - GLYCOPOISE (Glycosylation: Programmes for Observation, Inhibition and Structure-based Exploitation of key carbohydrate-active enzymes)
The development of new approaches to dissect the diverse and wonderful roles for carbohydrates in living cells is a major challenge for modern cell biology and biochemistry. The huge potential diversity of carbohydrates is reflected in a multiplicity of function for glycans; in addition to acting as energy sources, carbohydrates play central roles in cell and organism structure, communication (carbohydrates are “the language of the cell”) and signalling. The GlycoPOISE projects tackled key scientific challenges in mammalian glycoscience through a combination of 3-D structure, enzymology and subsequent application of chemical probes to living cells.
The Glycopoise program delivered a wealth of three-dimensional structures for key enzymes involved in glycobiology in humans; those where function was linked to disease: lysosomal storage diseases (such as Gaucher, Fabry and Pompe), viral invasion (such as Dengue) and enzymes involved in cancer for which compounds are in human clinical trial. Furthermore, we were able to dissect the chemical mechanism of these enzymes, to provide fundamental academic insight which acted as the foundation to deliver new enzyme inhibitors and coloured chemical probes to study the cellular biology of these enzymes. We obtained models and tools to diagnose and study the relevant diseases. Whilst we have focussed on these key enzymes and diseases, Glycopoise developed a conceptual workflow that is now being rolled-out to other enzyme classes: as tools to study human and organismal biology, as probes and diagnostics for disease and as tools to discover and characterize industrial enzymes in a dynamic manner.
The Glycopoise program delivered a wealth of three-dimensional structures for key enzymes involved in glycobiology in humans; those where function was linked to disease: lysosomal storage diseases (such as Gaucher, Fabry and Pompe), viral invasion (such as Dengue) and enzymes involved in cancer for which compounds are in human clinical trial. Furthermore, we were able to dissect the chemical mechanism of these enzymes, to provide fundamental academic insight which acted as the foundation to deliver new enzyme inhibitors and coloured chemical probes to study the cellular biology of these enzymes. We obtained models and tools to diagnose and study the relevant diseases. Whilst we have focussed on these key enzymes and diseases, Glycopoise developed a conceptual workflow that is now being rolled-out to other enzyme classes: as tools to study human and organismal biology, as probes and diagnostics for disease and as tools to discover and characterize industrial enzymes in a dynamic manner.