We are part of the Department of Chemistry which is part of the School of Natural Sciences.
Our lab is in the Department of Chemistry where we are part of the Organic Chemistry Research Group
Our research group has interests in synthetic and biological chemistry encompassing methodology, target synthesis, carbohydrate chemistry of various types, carbohydrate chemical biology, biocatalysis and heterocyclic chemistry.
Our group has developed new routes to complex heparin-related oligosaccharides, including the first gram scale routes to 12-mers, access to the longest heparin-related oligomers (up to 40-mer) and identifying single site sulfation control of in vitro and in vivo biological responses to synthetic long heparin-like molecules. This technology underpins ongoing routes to various oligosaccharide-related targets and new applications and techniques for their use for bio-interactions and potentially towards biomedical uses.
We also have interests in other carbohydrate targets through various collaborations (antibacterials, synthetic vaccine targets) and methodology for carbohydrate reactivity.
Interests in the group include organic synthesis but also with applications to chemical biology, and biophysical studies as well as materials chemistry.
We also have considerable experience in heterocyclic synthesis (polybenzimidazoles for example), 3D polyaromatics synthesis, dendrons and also in modified terpenoid synthesis through synthesis and some applications through biocatalysis, for example using enzymes to assist conversion of synthetic non-natural terpenoids to new chiral synths or polymer precursors. We hope to continue these programs and welcome applications from those interested in jointing our lab in those areas of applied organic synthesis.
Charity Activities in May 2022
Having run the Manchester 10K charity event the years before COVID, was hoping to get back in the first live one wit a University of Manchester 'Purple Wave' component this May. But a recurring knee failure means that isn't going to be possible. So, instead have signed dup to two charity May events can likely manage..
Centrepoint "122K steps in May". 122K=number of young people facing homelessness in the UK. The aim is to do 122K on 10 days on May. This will be slightly wobbly as still old walking with limp but its doable.
CRUK "100 push ups a day in May”. The title says it. Will aim to do at least 100 push ups per day, 7 days a week, in May.
Some Recent Highlight Research Papers
Example Papers of Research Areas
J. Org. Chem. 2019, 84, 15063-15078. 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. His sites below raised money for CRUK or Leukemia research and hoped would remain open indefinitely for direct donations in memory of his Dad, but just giving may longer allow donations. No llamas were harmed in the making of this haircut.