Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

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Ahmadipour, Sanaz, Wahart, Alice J. C., Dolan, Jonathan P., Beswick, Laura, Hawes, Chris S., Field, Robert A. ORCID: https://orcid.org/0000-0001-8574-0275 and Miller, Gavin J. (2022) Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase. Beilstein Journal of Organic Chemistry, 18. pp. 1379-1384. ISSN 1860-5397

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Abstract

Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its evaluation against GMD.

Item Type: Article
Additional Information: Funding Information: UK Research and Innovation (UKRI, Future Leaders Fellowship, MR/T019522/1) and the Engineering and Physical Sciences Research Council (EP/P000762/1) are thanked for project grant funding to GJM. Keele University are thanked for PhD studentship funding to AW and LB. Publisher Copyright: © 2022 Ahmadipour et al.
Uncontrolled Keywords: alginate,chemical probe,enzymatic synthesis,gdp-mannose dehydrogenase,sugar nucleotide,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1605
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
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Depositing User: LivePure Connector
Date Deposited: 03 Sep 2024 13:32
Last Modified: 02 Oct 2024 09:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/96469
DOI: 10.3762/bjoc.18.142

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