Glycomimetics: Useful Tools and Potential Therapeutics

S5.1 Glycomimetics
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 14:15 to 14:45
Speaker reference: 

Tanja Maria Wrodnigg1

1Glycogroup, Institute of Organic Chemistry, Graz University Of Technology, Graz, Austria

Glycomimetics are carbohydrate analogs with altered physical, physiological and/or biological properties based on structural changes compared to the respective parent compounds.[1] Iminosugars are glycomimetics with the ring oxygen being replaced by a basic trivalent nitrogen, which are very well known for their manifold applications as tools and therapeutics based on their interactions with glycoside processing enzymes. Representatives of this compound class find application in the elucidation of enzyme mechanisms and disease pathways.[2] For therapeutic purposes they are employed, for example, for the treatment of diabetes Type 2 (Miglitol®) and Gaucher disease Type 1 (Miglustat®). Other representatives have immunoregulating properties and anti-bacterial properties. Furthermore, some are considered to have potential for therapeutic disease management of Alzheimer’s as well as Parkinson disease. Recently, glycomimetics have been introduced as probes for activity based protein profiling (ABPP) of glycoprocessing enzymes.[3] Employing these small molecules, ABPP allows for evaluation of protein function on a global cellular level by rapid, sensitive, and selective detection and verification of protein activity rather than abundance.[4]

Our approach towards the design and syntheses of iminosugar based glycomimetics as potential therapeutics as well as probes for activity based protein profiling of glycoprocessing enzymes will be presented.

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  2. Hekmat, O.; He, S., Warren, R. A.; Withers, S. G. J. Proteome Res. 2008, 7, 3282-3292. Jiang, J.; Beenakker, T. J. M.; Kallemeijn, W. W.; van der Marel, G. A.; van den Elst; H., Codeé, J. D. C.; Aerts, J. M. F. G.; Overkleeft, H. S. Chem. Eur. J. 2015, 21, 10861-10869. Gandy, M. N.; Debowski, A. W.; Stubbs, K. A. Chem Commun. 2011, 47, 5037-5039.
  3. Willems, L. I.; Overkleeft, H. S.; Kasteren, S. I. Bioconj. Chem. 2014, 25, 1181-1191.
  4. Monitoring Glycans and their Interaction. Methods in Enzymology: Chemical Glycobiology Part B, Volume 598; Elsevier: 2018. Synthesis, Manipulations and Applications of Glycans. Methods in Enzymology: Chemical Glycobiology Part A., Volume 597; Elsevier: 2017.