Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides To Probe the GDP‑d‑Mannose Dehydrogenase from Pseudomonas aeruginosa

The chemoenzymatic synthesis of a series of C6-modified GDP-d-Man sugar nucleotides is described. This provides the first structure–function tools for the GDP-d-ManA producing GDP-d-mannose dehydrogenase (GMD) from Pseudomonas aeruginosa. Using a common C6 aldehyde functionalization strategy, chemic...

Full description

Saved in:
Bibliographic Details
Published in:Organic letters 2019-06, Vol.21 (12), p.4415-4419
Main Authors: Ahmadipour, Sanaz, Pergolizzi, Giulia, Rejzek, Martin, Field, Robert A, Miller, Gavin J
Format: Article
Language:English
Subjects:
Carbohydrate Conformation
Molecular Probes - chemical synthesis
Molecular Probes - chemistry
Nucleosides - chemical synthesis
Nucleosides - chemistry
Nucleotidyltransferases - analysis
Nucleotidyltransferases - metabolism
Pseudomonas aeruginosa - enzymology
Sugars - chemical synthesis
Sugars - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The chemoenzymatic synthesis of a series of C6-modified GDP-d-Man sugar nucleotides is described. This provides the first structure–function tools for the GDP-d-ManA producing GDP-d-mannose dehydrogenase (GMD) from Pseudomonas aeruginosa. Using a common C6 aldehyde functionalization strategy, chemical synthesis introduces deuterium enrichment, alongside one-carbon homologation at C6 for a series of mannose 1-phosphates. These materials are shown to be substrates for the GDP-mannose pyrophosphorylase from Salmonella enterica, delivering the required toolbox of modified GDP-d-Mans. C6-CH3 modified sugar-nucleotides are capable of reversibly preventing GDP-ManA production by GMD. The ketone product from oxidation of a C6-CH3 modified analogue is identified by high-resolution mass spectrometry.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.9b00967