LECNAC · Synthetic lectins for beta-GlcNAc: evaluation of their potential biological applications towards O-GlcNAc-modified proteins

Lectins are carbohydrate-binding proteins which play many roles in nature, and are important also as tools for biological research. For example, they are used to make fluorescent reagents which bind to, and thus identify, particular carbohydrate units, and also to make separation media which distinguish between differently glycosylated biomolecules. An important target for such reagents/media is beta-GlcNAc on serine or threonine (the O-GlcNAc protein modification). This moiety has been implicated in many biological processes and human diseases such as diabetes and neurobiological disorders. The lectins used to bind O-GlcNAc do not perform especially well, and the host group have shown that, remarkably, a designed “synthetic lectin” may be superior. The aim of the project is to explore this possibility, developing and testing biological tools (e.g. stains and separation media) based on the synthetic system. The research will involve international collaboration with five laboratories, two in Europe (Madrid and Leuven) and three in the US. The applicant will move from Spain to Bristol (UK) to carry out this research, while undergoing training in a variety of scientific and complementary skills (including during visits to two collaborating laboratories). The applicant plans a scientific career at the interface between supramolecular chemistry and biology (biosupramolecular chemistry). The project will expand his synthetic, organic and supramolecular chemical knowledge, introduce him to certain biological techniques (e.g. Western blotting, affinity chromatography and biological NMR), and encourage him to develop his independent scientific ideas. At the end of the Fellowship he will be well-positioned to apply for independent positions in the ERA. If successful, his research will have shown that synthetic receptors can complement proteins in performing complex and difficult molecular recognition tasks.