We are part of the Department of Chemistry and are based in the Manchester Institute of Biotechnology (MIB). Much of the work in the group involves organic synthesis. We are part of the Department of Chemistry's Synthesis and Chemical Biology Research Groups.
Our research group has interests in synthetic and biological chemistry encompassing methodology, target synthesis, carbohydrate chemistry of various types, biocatalysis and heterocycle chemistry. Our group has developed new routes to complex heparin-related oligosaccharides, and this technology underpins ongoing routes to various heparin-related targets. This includes patented key synthetic chemistry and commercial applications and licencing are currently being undertaken via UMIP.
Some Recent Highlight Research Papers
J. Org. Chem. 2019 in press. Jeanerret, R. A.; Dalton, C. E.; Gardiner J. M. "Synthesis of Heparan Sulfate- and Dermatan Sulfate-Related Oligosaccharides via Iterative Chemoselective Glycosylation Exploiting Conformationally-Disarmed [2.2.2] L-Iduronic Lactone Thioglycosides."
Chem.-Eur. J. 2019. 25, 2983-2988. I. S.; Toogood, H. T.; Johannisen, L. O.; Scrutton, N. S.; Gardiner, J. M. "C3 and C6 Modification-specific OYE biotransformations of synthetic carvones and sequential BVMO chemoenzymatic synthesis of chiral caprolactones."
J. Nat. Prod. 2018, 81, 1546–1552. DOI: 10.1021/acs.jnatprod.7b01026. Ní Cheallaigh, A.; Toogood, H.; Mansell, D. J.; Lygidakis, A.; Tait, S.; Scrutton, N. S.; Gardiner, J. M. "Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway"
ChemPhysChem 2016, 21, 3442-3446. DOI: 10.1002/cphc.201600750 Dalton,C. E.; Quinn,S. D.; Rafferty,A.; Morten,M. J.; Gardiner,J. M.; Magennis, S. W. “Single-molecule fluorescence detection of a synthetic heparan sulfate disaccharide.”
Observabability of synthetic single saccharides and their microscopic encapsulation.
ACS Catal. 2017, 7, 6268−6282. DOI: 10.1021/acscatal.7b01924. Karuppiah, V.; Ranaghan, K. E.; Leferink, N. G. H.; Johannissen, L. O.; Shanmugam, M.; Ní Cheallaigh, A.; Bennett, N. J.; Kearsey, L. J.; Takano, E.; Gardiner, J. M.; van der Kamp, M. W.; Hay, S.; Mulholland, A. J.; Leys, D.; Scrutton, N. S. “Structural Basis of Catalysis in the Bacterial Monoterpene Synthases Linalool Synthase and 1,8-Cineole Synthase.”
Synthetic site-specifically fluorinated substrate helps provide structural insight into enzymes involves in cyclization to terpenoids.
Angewandte Chemie 2016, 55, 9596 –9600. DOI: 10.1002/ange.201603785. Lygidakis, A.; Ní Cheallaigh, A.; Karuppiah, V.; Hoeven, R.; Leys, D.; Gardiner, J. M.; Toogood, H. S.; Scrutton, N. S. “Pinpointing a mechanistic switch between ketoreduction and ‘ene’-reduction in short chain dehydrogenases/reductases.”
In collaboration with Scrutton and Leys labs work using synthetic substrates and site-modified enzymes has identified an unusual mechanistic switch from reduction to ene reaction.
Org. Biomol. Chem. 2015, 13, 11208-19. Miller, G. J.; Broberg, K R.; Rudd, C.; Helliewell, M. R.; Jayson, G. C.; Gardiner, J. M. “A latent reactive handle for functionalising heparin-like and LMWH deca- and dodecasaccharides.”
Gavin’s work on synthesis of heparan sulfate and LMWH-type 10-mers and 12-mers bearing conjugation tag has been published, complimenting this lab's recent papers on longer synthetic heparins.
Chemical Science 2015, 6, 6158-6164. Hansen, S. U.; Miller, G. J.; Cliff, M. J.; Jayson, G. C.; Gardiner, J. M. “Making the longest sugars: A chemical synthesis of heparin-related n oligosaccharides from 16-mer to 40-mer.” Our synthesis of the longest synthetic heparin-related oligosaccharides by using our tetrasaccharide block strategy, and the use of new NMR methods to support and quantify anomeric integrity, is now out. A further report on this paper will be published. *PAPER GOES HOT ARTICLE* July ‘hot’ article at ChemSci and subject of a Chemistry World highlight article.
Chem. Commun. 2015, 51, 13846-13849. Jayson, G. C.; Hansen, S. U.; Miller, G. J.; Cole, C. L.; Rushton, G.; Avizienyte, E.; Gardiner, J. M. “Synthetic heparan sulfate dodecasaccharides reveal single sulfation site interconverts CXCL8 and CXCL12 chemokine biology.”
This reports our large scale synthesis of a programmed heparin dodecassacharide and shows that single sulfate location regulates both in vitro and in vivo biology mediated by two biomedically-important chemokines. This enables future programmed synthesis of site-specific drug candidates, and work in this area is ongoing in colaboration with the Jayson lab at the Paterson Institute/Christie Hospital.
ACS Synthetic Biology 2015, 4, 1112-1123. ASAP. DOI:10.1021/acssynbio.5b00092. Toogood, H. S.; Ní Cheallaigh, A.; Tait, S.; Mansell, D.; Jervis, A.; Lygidakis, A.; Humphreys, L.; Takano, E.; Gardiner, J. M.; Scrutton, N. S. “Enzymatic Menthol Production: One-Pot Approach Using Engineered Escherichia coli.”
Combining synthetic substrates and genetically multi-gene engineered cell-factories for high value terpenoid synthesis.
Nature Commun. 2013, 4, 415. Hansen, S. U.; Miller, G. J.; Cole. C.; Rushton, G.; Avizientye, E.; Jayson, G. C.; Gardiner, J. M. “Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies.”
Our paper on a new tetrasaccharide-based synthesis of a dodecassaccharide, developing new end-labelling chemistry for pharmokinetics studies was published in Nature Commun.
Chemical Science 2013, 4, 3218-3222. Miller, G. J.; Hansen, S. U.; Cole. C.; Avizientye, E.; Rushton, G.; Jayson, G. C.; Gardiner, J. M. "Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF165-mediated endothelial cell functions.”
Synthesis of various long GAG fragments used to probe he effects of O6 sulfation of biomedically important targets for oligsaccharides.
Chem. Commun. 2014, 5000 - 5002. Kadirvel, M.; Fanimarvasti, F.; Forbes, S.; McBain, A.; Gardiner, J. M.;* Brown, G. D.;* Freeman, S.* “Inhibition of quorum sensing and biofilm formation in Vibrio harveyi by 4-Fluoro-DPD; a novel potent inhibitor of AI-2 signalling.”
New synthetic analogues of bacterial quorum signalling molecules lead to a new potent antibacterial lead.
CRUK and Leukemia Research Sponsorship
Prof Peter Gilbert - an academic at Manchester - died of pancreatic cancer a few days before his son’s 11th birthday. A few months later David’s teenage cousin died of leukemia. Peter’s son, David had his hair shaved off in a special School assembly to raise support for cancer charities. If you want to sponsor CRUK or Leukemia research through him please visit his sites below. They remain indefinitely open for direct donations in memory of his Dad - so far, his sponsorship has raised over £1300. No llamas were harmed in the making of this haircut.