11:30
Dr Ben Schumann: Sugars and Therapeutics
12:00
Main Visiting Speaker – Professor M. Carmen Galan: Novel synthetic probes as cancer diagnostic tools and therapeutics
Abstract:
The Galan group is interested in the development of novel synthetic tools for biological research particularly in the areas of diagnostic tools and drug delivery. Herein, I will report our latest developments on the synthesis and application of novel synthetic probes in two distinct but related areas.
Part 1. O-Glycosylation is a ubiquitous post-translational modification that is highly dynamic and responsive to cellular stimuli through the action of the cycling enzymes. Expression of specific O-glycans is linked to changes in gene expression in, for example, inflammatory bowel disease, cystic fibrosis and several types of cancer.[1] Glycan coated-nanoparticles constitute a good bio-mimetic model of carbohydrate presentation at the cell surface and provide a powerful tool to screen for protein carbohydrate interactions and consequently for the identification of carbohydrate receptors or ligands associated with many inter- and intracellular recognition processes associated to disease. In this area, our group has prepared structurally defined multivalent O-glycan probes for the screening of O-glycosylation-linked interactions in live cells in the areas of cancer and bacteria detection.[2]
Part 2. The development of small molecule ligands that bind to G4 and regulate its stability and structure has been recognized as a valid target for the development of anti-cancer therapeutics. Towards this end, we have designed, synthesised and evaluated a unique series of G4-binding ligands which have been shown to induce unique selectivity and exceptionally high thermal stabilisation in G4 DNA and exhibit nanomolar toxicity towards cervical cancer cells. Furthermore we demonstrated that a stiff-stilbene ligand can act as photo-responsive fuel for the conformational switching of G4 DNA using light as an external stimulus.[3]
[1] M. C. Galan*, D. Benito-Alifonso and G. M. Watt. Carbohydrate Chemistry in Drug Discovery. Org. Biomol. Chem. (2011), 9 (10), 3598 – 3610.
[2] a) Benito-Alifonso, D.; Tremel, S.; Hou, B.; Lockyear, H.; Mantell, J.; Fermin, D. J.; Verkade, P.; Berry, M.; Galan, M. C. Angew Chem Int Edit 2014, 53, 810. b) S. A. Hill, D. Benito-Alifonso, D.J. Morgan, S.A. Davis, M. Berry, M. C. Galan* Nanoscale 2016 , 8, 18630. c) D. Benito-Alifonso, B. Richichi, V. Baldoneschi,M. Berry,M. Fragai, G. Salerno, M. C. Galan,* and C. Nativi* “ACS Omega 2018, 3, 9822. d) S. A. Hill, D. Benito-Alifonso, S. A. Davis, D. J. Morgan, M. Berry, and M. C. Galan* Scientific Reports, 2018, 8,12234. e) T. A. Swift, M. Duchi, S. A. Hill, D. Benito-Alifonso, R. L. Harniman, S. Sheikh, S. A. Davis, A. M. Seddon, H. M. Whitney, M. C. Galan* and T. A. A. Oliver*. Nanoscale, 2018, 10, 13908.
[3] a) S. T. G. Street, D. N. Chin, G. J. Hollingworth, M. Berry, J. C. Morales* and M. C. Galan*. Chem. Eur. J. 2017, 23, 6953. b) M.P. O’Hagan, S. Haldar, M. Duchi, T.A.A. Oliver, A. J. Mulholland, J.C. Morales and M.C. Galan*. Angew. Chem. Int. Ed., 2019, 131, 1
Biography:
M. Carmen Galan received her B.S. degree in chemistry from Universidad de Alicante, Spain. She was awarded a Socrates-Erasmus grant to pursue an MPhil in Pure and Applied Chemistry at the University of Strathclyde, Glasgow, under the supervision of Prof. P.J. Hall and Dr. L.E.A. Berlouis. She received her Ph.D. in Organic Chemistry from the Complex Carbohydrate Research Center at The University of Georgia, USA, under the supervision of Prof. Geert-Jan Boons, where she carried out research in the field of carbohydrates. She then moved to California to pursue post-doctoral research with Prof. Chi-Huey Wong at The Scripps Research Institute. After that, she continued her post-doctoral training at Massachussetts Institute of Technology with Prof. Sarah O’Connor.
Carmen returned to the UK in October 2006 on a lecturership in the School of Chemistry. In 2008 she became a Royal Society Dorothy Hodgkin fellow and from 2012-2017 she held a five year EPSRC Career Acceleration Fellowship. She currently holds and ERC consolidator award (from 2015) and since August 2017, the position of Professor in the School of Chemistry. In 2017, Carmen was awarded the RSC Carbohydrate Award.