Organic Chemistry Seminar: Fundamental Insights into Glycosylation Reactions as Basis for Automated Glycan Assembly, Vaccines, Therapeutics and Diagnostics

Abstract:

Following fundamental discoveries concerning all aspects of glycosylation reactions,1 automated glycan assembly (AGA)2 has developed into a reliable technology3 that allows for preparation of diverse oligo- and polysaccharides4 on a solid support employing a synthesizer.5 Access to ever more complex glycans enables investigations into the structure and function of polysaccharide materials, vaccines and diagnostics. AGA gave rise to molecular glycobiology. Placing synthetic glycans on surfaces gave rise to glycan microarrays6 that were used for diagnostic purposes and to discover the cause of autoimmune diseases. 7

Vaccine programs aimed at protection from most bacteria and fungi found on the WHO list of the most critical microbial threats are underway. A vaccine candidate against C. difficile successfully completed Phase 1 human clinical trials.8 Vaccine candidates against a host of other pathogens are currently in preclinical evaluation. Synthetic oligosaccharides have given rise to monoclonal antibodies to kill cancer cells. 9 An antibody-drug conjugate is being prepared for human clinical trials.

References

1. Plante, O.J.; Andrade, R.B.; Seeberger, P.H. Organic Letters 1999, 1, 211-214.

2. Plante, O.J.; Palmacci, E.R.; Seeberger, P.H.; Science 2001, 291, 1523.

3. Guberman, M.; Seeberger, P.H.; J. Am. Chem. Soc., 2019, 141, 5581.

4. Joseph, A.; Pardo-Vargas, A.; Seeberger, P.H.; J. Am. Chem. Soc., 2020, 142, 8561.

5. Hahm, H.S.; Schlegel, M.K.; Hurevich, M.; Eller, S.; Schuhmacher, F.; Hofmann, J.; Pagel, K.; Seeberger, P.H.; Proc Nat Acad Sci USA, 2017, 114, E3385.

6. Geissner, A.; Seeberger, P.H. Ann Rev Anal Chem 2016, 9, 223.

7. Pröbstel, A.-K.; …..Seeberger, P.H.; Gommerman, J.L.; Schirmer, L.; Wilson, M.R.; Baranzini, S.E.; Science Immunology 2020, 5, eabc7191.

8. Martin, C.E.; Broecker, F.; Oberli, M.A.; …..Seeberger, P.H.; J. Am. Chem. Soc. 2013, 135, 9713; Broecker, F.; Hanske, J.;…. Seeberger, P.H.; Nature Comm. 2016, 7, 11224; Broecker, F.; Martin, C.E.; Anish, C.; Seeberger, P.H.; Cell Chem. Bio. 2016, 23, 1014.

9. Goerdeler, F.; Reuber, E.; Lühle, J.; Leichnitz, S.; Freitag, A.; Nedielkov, R.; Möller, H.; Seeberger, P.H.; Moscovitz, O.; ACS Cent. Sci. 2023, 9, 1111.

Event Organizer: Dr. Muhammad Jbara