Imidazolium-based tags as probes to harness glycosyltransferase activity in human breast milk

S9.2 Chemical tools for glycosyl transferases
Location (hall): 
Start/end time: 
Thursday, July 4, 2019 - 15:30 to 15:45

Hélène Ledru1, Sandra Medina1, Imke Sittel1, Carmen Galan1

1University Of Bristol, Bristol, United Kingdom

Carbohydrates have become important targets for novel therapeutics[1], due to their diversity in nature and their involvement in a myriad of biological processes, such as cell-cell communication, fertilisation, immunity to pathogenic attack.[2] However only limited carbohydrate-based drugs have been developed, mainly due to the lack of efficient methods to obtain structurally defined samples by either chemical synthesis or isolation, for biological screening.

Our group has developed imidazolium-based Tags (ITags) for the chemical and enzymatic synthesis of oligosaccharide whereby the ITag serves a dual purpose as soluble purification support and as mass spectrometry reporter which eliminates the need for expensive radioactive or fluorescent probes, and to facilitate product isolation, as a purification handle.[3,4] (see Figure 1) These ITags have been shown to be compatible with several glycosyltransferases.

Herein, we report the synthesis of a new class of ITag labels, which can be used to harness the natural biosynthetic machinery present in human breast milk (i.e. glycosyltransferases) to access biologically important oligosaccharides.

Figure 1. General scheme for ITag-supported synthesis and reaction monitoring[3,4]

  1. Galan, M. C., Benito-Alifonso, D., Watt, G. M., Carbohydrate chemistry in drug discovery. Org. Biomol. Chem. 2011, 9, 3598-3610
  2. Linden, S. K., Sutton, P., Karlsson, N. G., Korolik, V., McGuckin, M. A., Mucins in the mucosal barrier to infection. Mucosal Immunology 2008, 1, 183-197. 
  3. Tran, A.-T., Burden, R., Racys, D. T., Galan, M. C., Ionic catch and release oligosaccharide synthesis (ICROS). Chem. Commun. 2011, 47, 4526-4528.
  4. a) Galan, M. C., Tran, A. T., Bromfield, K., Rabbani, S., Ernst, B., Ionic-liquid-based MS probes for the chemo-enzymatic synthesis of oligosaccharides. Org. Biomol. Chem. 2012, 10, 7091-7097. b) Sittel, I., Galan, M. C., Chemo-enzymatic synthesis of imidazolium-tagged sialyllactosamine probes. Bioorg. Med. Chem. Lett. 2015, 25, 4329-4332. c) Sittel, I., Galan, M. C., Imidazolium-labeled glycosides as probes to harness glycosyltransferase activity in human breast milk. Org. Biomol. Chem. 2017, 15, 3575-3579.