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

Ahmadipour, Sanaz; Wahart, AJC; Dolan, JP; Beswick, Laura; Hawes, CS; Field, RA; Miller, GJ

doi:10.3762/bjoc.18.142

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

Ahmadipour, Sanaz; Wahart, AJC; Dolan, JP; Beswick, Laura; Hawes, CS; Field, RA; Miller, GJ

Authors

Sanaz Ahmadipour

AJC Wahart

Jonathan Dolan j.dolan@keele.ac.uk

Laura Beswick

Chris Hawes c.s.hawes@keele.ac.uk

RA Field

Gavin Miller g.j.miller@keele.ac.uk

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-?-mannose and its evaluation against GMD.

Journal Article Type	Letter
Acceptance Date	Sep 19, 2022
Publication Date	Sep 30, 2022
Journal	Beilstein Journal of Organic Chemistry
Print ISSN	1860-5397
Publisher	Beilstein-Institut
Peer Reviewed	Peer Reviewed
Volume	18
Pages	1379 - 1384
DOI	https://doi.org/10.3762/bjoc.18.142
Keywords	alginate; chemical probe; enzymatic synthesis; GDP-mannose dehydrogenase; sugar nucleotide
Publisher URL	https://www.beilstein-journals.org/bjoc/articles/18/142