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Glycobiology, the structure and chemical reactions of sugars in the human body, can play a role in disease development. It is an emerging but complex field. In the SWEETOOLS project, Dr Milan Vrabel is supported by the European Research Council (ERC). The project is an attempt to combine chemical synthesis with bioengineering to build hybrid biochemical structures. His team at the Institute of Organic Chemistry and Biochemistry (IOCB) in Prague will use both selective biologic tools for protein-related study and highly targeted small-molecule ‘warheads’.
Biologics are copies or optimised versions of human proteins which are engineered in laboratories. These genetically modified cells are grown to bind selectively to specific cell receptors. For example, they may be able to bind only to receptors of cancer cells, identifying and fighting specific abnormal cells without harming other healthy ones. Such treatments could mean fewer side effects than are caused by their more established chemical counterparts, such as chemotherapy.
Chemically synthesised drugs would still play a vital role in the process. These so-called small-molecule warheads can be used to deactivate targets (diseased cells, for example) rapidly and selectively.
But for this to happen, Vrabel will need to develop a new class of bioconjugates – a chemical strategy to form a stable link between two molecules, at least one of which is a biomolecule – to be used as delivery systems that will bind the ‘warheads’ exclusively to sugar processing enzymes. This would enable researchers to further explore the role sugars play in both the development and treatment of disease.
The research could help advance the engineering of novel therapies and vaccines for the targeted treatment of a wide range of diseases which currently have no effective cure. One example on which the SWEETOOLS team is focusing is the development of biomedicines to combat influenza infection.