1378357-82-4Relevant academic research and scientific papers
Chemical synthesis of C6-Tetrazole ?-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate
Dimitriou, Eleni,Miller, Gavin J.
supporting information, p. 1527 - 1532 (2021/07/26)
Alginate is a biocompatible and industrially relevant polysaccharide that derives many of its important properties from the charged carboxylate groups within its polyuronic acid backbone. The design and inclusion of isosteric replacements for these carbox
Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides to Probe the GDP- d -Mannose Dehydrogenase from Pseudomonas aeruginosa
Ahmadipour, Sanaz,Pergolizzi, Giulia,Rejzek, Martin,Field, Robert A.,Miller, Gavin J.
, p. 4415 - 4419 (2019/06/17)
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.
NEW HEPTOSE DERIVATIVES AND BIOLOGICAL APPLICATIONS THEREOF
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, (2012/06/16)
Compounds having the general formula (I) and their biological applications.
Systematic synthesis of inhibitors of the two first enzymes of the bacterial heptose biosynthetic pathway: Towards antivirulence molecules targeting lipopolysaccharide biosynthesis
Durka, Maxime,Tikad, Abdellatif,Périon, Régis,Bosco, Michael,Andaloussi, Mounir,Floquet, Stéphanie,Malacain, Elodie,Moreau, Fran?ois,Oxoby, Mayalen,Gerusz, Vincent,Vincent, Stéphane P.
supporting information; experimental part, p. 11305 - 11313 (2011/10/19)
L-Heptoses (L-glycero-D-manno-heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D-glycero-D-manno-heptopyranose 7-phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1-, 2-, 6- and 7-positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6- and 7- positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D-glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC50=34 μM) and HldE (IC50=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence. Copyright
