Modifications Matter: Probing the Effects of Glycosylation on Peptide and Protein Activity

Session: 
S2.3 Synthetic glycoproteins
Code: 
KL2.3
Location (hall): 
Galactose
Start/end time: 
Monday, July 1, 2019 - 14:15 to 14:45
Speaker reference: 
Richard
Payne

Richard Payne1

1The University of Sydney, Sydney, Australia

Glycosylation is the most common co- and post-translational modification of polypeptides, with over 50% of human proteins predicted to display covalently bound glycans. Glycoproteins are known to mediate an array of biological recognition events and a number of recently approved biopharmaceuticals contain carbohydrate chains (or carbohydrate mimics) that are critical for activity and/or stability.¹ In addition, aberrant glycosylation is associated with a number of disease states including autoimmune diseases and cancer.

The non-templated enzymatic glycosylation process leads to heterogeneous mixtures of isoforms when glycoproteins are produced in eukaryotic expression systems that hinders the ability to study glycoprotein structure and function in a meaningful way. This has led to significant demand for new tools and technologies to facilitate access to homogeneous glycopeptides and glycoproteins to interrogate the role of individual carbohydrate modifications on structure and function. This talk will outline the use of synthetic technologies developed in our laboratory to access homogeneously glycosylated peptides and proteins for structure-function studies.² The synthesis and evaluation of glycopeptide hormones,³ bacterial glycoproteins,⁴ cytokines and thrombin-inhibiting glycoproteins from medicinal leeches⁵ will be highlighted.

References: 
  1. G. Walsh, R. Jefferis, Nat. Biotechnol. 2006, 24, 1241.
  2. S. Kulkarni, E. E. Watson, B. Premdjee, R. J. Payne, Nat. Rev. Chem. 2018, 2, 0122.
  3. L. Corcilius, A. H. Hastwell, M. Zhang, J. Williams J. P. Mackay, P. M. Gresshoff, B. J. Ferguson, R. J. Payne, Cell Chem Biol. 2017, 24, 1347.
  4. S. Wang, L. Corcilius, P. P. Sharp, A. Rajkovic, M. Ibba, B. L. Parker, R. J. Payne, Chem Sci. 2017 8, 2296.
  5. Y. S. Hsieh, B. L. Wilkinson, L. C. Wijeyewickrema, R. N. Pike, R. J. Payne, Angew. Chem. Int. Ed. 2014, 53, 3947.

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