Base-modified GDP-mannose derivatives and their substrate activity towards a yeast mannosyltransferase

Collier, Alice and Wagner, Gerd K. (2017) Base-modified GDP-mannose derivatives and their substrate activity towards a yeast mannosyltransferase. Carbohydrate Research, 452. pp. 91-96. ISSN 0008-6215

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We have previously developed a new class of inhibitors and chemical probes for glycosyltransferases through base-modification of the sugar-nucleotide donor. The key feature of these donor analogues is the presence of an additional substituent at the nucleobase. To date, the application of this general concept has been limited to UDP-sugars and UDP-sugar-dependent glycosyltransferases. Herein, we report for the first time the application of our approach to a GDP-mannose-dependent mannosyltransferase. We have prepared four GDP-mannose derivatives with an additional substituent at either position 6 or 8 of the nucleobase. These donor analogues were recognised as donor substrates by the mannosyltransferase Kre2p from yeast, albeit with significantly lower turnover rates than the natural donor GDP-mannose. The presence of the additional substituent also redirected enzyme activity from glycosyl transfer to donor hydrolysis. Taken together, our results suggest that modification of the donor nucleobase is, in principle, a viable strategy for probe and inhibitor development against GDP-mannose-dependent GTs.

Item Type: Article
Uncontrolled Keywords: mannosyltransferase,ndp-mannose,donor analogue,substrate
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: Pure Connector
Date Deposited: 23 Sep 2017 05:08
Last Modified: 22 Oct 2022 03:11
DOI: 10.1016/j.carres.2017.09.010

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