Every living cell is covered in a coating of complex carbohydrates and so anything that approaches the cell membrane must descend through this forest of carbohydrates. The interaction of these carbohydrates with enzymes and proteins is an essential part of healthy cell activity but at the same time many parasites, viruses, bacteria and their toxins exploit these mechanisms to colonise tissues and enter cells. Understanding such processes can lead to new methods for diagnosis and treatment of infectious diseases. In addition the carbohydrate coating of cells changes when they become cancerous so that many of their carbohydrate structures become over-expressed, or uniquely expressed making them useful cancer biomarkers that can be exploited for diagnosis, or targeted immunotherapies/drug delivery.
Our growing understanding of glycoscience, and the advent of chemical and synthetic biology methodologies, presents an opportunity to redesign and synthesise these biological components for diverse analytical, diagnostic and targeted therapeutic applications. This is the field of Synthetic Glycobiology.
synBIOcarb brings together a diverse team of chemists, structural biologists, biophysicists, cell biologists and protein engineers who are pioneering the development of Synthetic Glycobiology, and four SMEs that are leading industrial innovation in glycoscience and protein engineering.
During the project we aimed to:
1. further our fundamental understanding of structure-activity relationships for protein-carbohydrate interactions. In particular, how changes in the architecture of lectins affects their binding selectivity and ability to interact with, bend and fuse membranes together.
2. expand our toolbox of Synthetic Glycobiology building blocks that can be used to functionalise complex surfaces including supported bilayers, GUVs, living cells. This work includes chemical and enzymatic synthesis of new glycosylated lipidated peptides and use of bioorthogonal coupling to attach lectins to surfaces in defined orientations.
3. move Synthetic Glycobiology towards practical applications in diagnostic and analytical devices through developing methods to detect tumour associated cancer antigens and specific glycans important in the quality control of pharmaceutical glycoproteins.
4. move Synthetic Glycobiology towards practical applications in cell targeting and drug delivery, through investigation of how lectins attached to polymers, other lectins, or antibody fragments/mimetics, either through bioorthogonal coupling or genetic fusion, can be used to target cancer cells for drug delivery or immunotherapies.
