Cyclopropene Derivatives of Aminosugars for Metabolic Glycoengineering

Session: 
S2.4 Sugar biosynthesis
Code: 
FL2.4.5
Location (hall): 
Fucose
Start/end time: 
Monday, July 1, 2019 - 15:35 to 15:40
Jessica
Hassenrück

Jessica Hassenrück1, Valentin Wittmann1

1Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany

Metabolic glycoengineering (MGE) is a valuable tool to investigate and visualize cellular glycans. In this technique, unnatural carbohydrates, carrying a chemical reporter group, are incorporated into glycoconjugates and can then be visualized using a bioorthogonal ligation reaction, such as the inverse-electron-demand Diels-Alder (DAinv) reaction. Besides terminal alkenes [1] and norbornenes [2], cyclopropenes [3] proved to be especially valuable chemical reporter groups for MGE. In the past, three cyclopropene-modified mannosamine derivatives (Ac₄ManNCyc [3a], Ac₄ManNCyoc [3b], and Ac₄ManNCp [3c]) have been reported. However, a direct comparison of the performance of these three compounds in MGE has not been investigated.

Here, we present a comparative study of these mannosamine derivatives focusing on their reaction kinetics, acceptance by the enzymatic machinery, and the overall cell-surface staining intensity [4]. We determined second-order rate constants of the compounds in a DAinv reaction and the efficiency by which the sugars are incorporated into cellular sialic acids. Inspired by these results, we developed novel glucosamine and galactosamine derivatives featuring a cyclopropene moiety and explored their behavior in MGE.

References: 
  1. a) Niederwieser, A.; Späte, A.-K.; Nguyen, L. D.; Jüngst, C.; Reutter, W.; Wittmann, V. Angew. Chem., Int. Ed. 2013, 52 (15), 4265-4268; b) Späte, A.-K.; Schart, V. F.; Schöllkopf, S.; Niederwieser, A.; Wittmann, V. Chem. Eur. J. 2014, 20 (50), 16502-16508; c) Dold, J. E. G. A.; Pfotzer, J.; Späte, A.-K.; Wittmann, V. ChemBioChem 2017, 18 (13), 1242-1250.
  2. Späte, A.-K.; Dold, J. E. G. A.; Batroff, E.; Schart, V. F.; Wieland, D. E.; Baudendistel, O. R.; Wittmann, V. ChemBioChem 2016, 17 (14), 1374-1383.
  3. a) Cole, C. M.; Yang, J.; Šečkutė, J.; Devaraj, N. K. ChemBioChem 2013, 14 (2), 205-208; b) Späte, A.-K.; Bußkamp, H.; Niederwieser, A.; Schart, V. F.; Marx, A.; Wittmann, V. Bioconjugate Chem. 2014, 25 (1), 147-154; c) Xiong, D.-C.; Zhu, J.; Han, M.-J.; Luo, H.-X.; Wang, C.; Yu, Y.; Ye, Y.; Tai, G.; Ye, X.-S. Org. Biomol. Chem. 2015, 13 (13), 3911-3917.
  4. J. Hassenrück, V. Wittmann, Beilstein J. Org. Chem. 2019, 15, accepted.

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