Synthetic Glyco-Tools For Exploring And Exploiting The Glycome

Abstract

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.

The stereoselective synthesis of glycosides remains one of the biggest challenges in carbohydrate chemistry. The chemical synthesis of complex carbohydrates generally involves the coupling of a fully protected glycosyl donor bearing a leaving group at its anomeric centre, with a suitably protected glycosyl acceptor (R-OH). In many instances, these reactions lead to a mixture of two stereoisomers. Towards this goal, our group has endeavoured to develop catalytic and stereoselective methods to address this important synthetic challenge. Recent years have seen a steady increase in the application of transition metal catalysis applied to oligosaccharide synthesis, since the reaction conditions are mild and the careful choice of catalyst can offer significant improvements over traditional methods in terms of atom economy, high yields and control of anomeric selectivity.

Herein, we will discuss the application of transition metal catalysis in the stereoselective synthesis of deoxy glycosides, including the a,a-stereoselective synthesis of trehalose derivates and their application as selective probes of bacteria detection. Moreover, I will also disclose recent development of a rapid bacteria screening strategy based on carbohydrate-functionalized polystyrene microspheres. Using this assay, we identified selective binding of C-2 linked arabinose moieties immobilized on a microbead surface to Staphylococcus aureus, a Gram-positive pathogenic bacterium of which antimicrobial-resistant strains are widespread and problematic.

Biography

M. Carmen Galan is currently a Professor of Organic and Biological Chemistry in the Chemistry Department at the University of Bristol and the School Research Director. In 2014, she was awarded an ERC consolidator grant. Prior to that, she held an EPSRC Career Acceleration Fellowship (2012-2017), a Royal Society Dorothy Hodgkin Fellowship (2008-2012) and a lectureship (2006-2008) within the same School. Her internationally recognized research spans from medicinal chemistry, carbohydrate synthesis, catalysis, functional nanomaterials to biological applications in the areas of cancer, antimicrobials and plant nanobionics. In 2017, she was awarded the RSC Dextra Carbohydrate Chemistry award in recognition of her research into new synthetic methodologies for oligosaccharide synthesis and the development of novel glycoconjugate probes. In 2021 she received the RSC Jeremy Knowles award for the development of bioinspired synthetic probes for the targeting and regulation of cellular processes and in 2022 she was awarded the SRUK Merit award for her contributions to science and the impact of her work to the wider community. More recently, her contribution to the field of carbohydrate chemistry have been recognized and she has been awarded the 2025 ACS Melville L. Wolfrom Award.  In addition to her academic duties, she is the Editor-in-Chief of Carbohydrate Research. She is also the co-founder and co-Director of CDotBio Ltd a university of Bristol spin out.