Flagship three - Chemical Biology
Leader: Antony Fairbanks
Chemical Biology involves the application of chemical techniques, tools, analyses and often compounds produced through synthetic chemistry to the study and manipulation of biological systems.
The vast majority of world-leading chemistry departments have a strong research presence in the chemical biology field, as the tools of synthetic organic chemistry are applied directly to contemporary biological problems.
The creation of this flagship aims to synergise synthetic chemistry capabilities, both at UC and elsewhere in New Zealand, with topical and interesting biology problems. In particular, the aims are to use synthetic molecules and chemistry techniques to both further our understanding and modulate highly complex biomolecular interactions.
BIC PI Antony Fairbanks and his team have been engineering ENGase (endo-β-N-acetylglucosaminidases) enzymes as biocatalysts for the production of homogenous glycopeptides and glycoproteins. They published two recent standout publications1,2 in this area. In Angewandte Chemie they report the first-ever production of a glycoprotein bearing mannose-6-phosphate residues using ENGases. Mannose-6-phosphate is an important biomarker, the addition of which results in protein transport to the lysosome.
This project, which has significant implications for the development of better treatments for lysosomal storage disorders by enzyme replacement therapy, has just been supported by the awarding of $870,000 of Marsden funding. This will see Antony collaborate with Callaghan Innovation’s UC-based Protein Science and Engineerging Team; along with Professor Fran Platt, University of Oxford, and Professor Matthieu Sollogoub from the Pierre and Marie Curie University, Paris, France.
The second publication in Chemical Science relates to a collaborative project undertaken with the research groups of Margaret Brimble and Rod Dunbar (University of Auckland). In this landmark study ENGase enzymes were used to produce glycopeptide vaccine candidates decorated with homogeneous high-mannose glycans, which they then demonstrated were more effectively taken up by dendritic cells than non-glycosylated versions.
1. P .Priyanka, T.B. Parsons, A. Miller, F.M. Platt, and A.J. Fairbanks, “Chemoenzymatic synthesis of a phosphorylated glycoprotein.” Angewandte Chemie International Edition vol. 55, no. 16, pp. 5058-5061, March 2016.
2. J.D. McIntosh, M.A. Brimble, A.E.S. Brooks, P.R. Dunbar, R. Kowalczyk, Y. Tomabechi, and A.J. Fairbanks, “Convergent chemo-enzymatic synthesis of mannosylated glycopeptides; targeting of putative vaccine candidates to antigen presenting cells” Chemical Science, vol. 6, no. 6, pp. 4636-4642, May 2015.