Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide

Pseudomonas aeruginosa is a highly prevalent gram-negative bacterium that is becoming more difficult to treat because of increasing antibiotic resistance. As chemotherapeutic treatment options diminish, there is an increased need for vaccines. However, the creation of an effective P. aeruginosa vacc...

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Autores principales:	Anshupriya Si, Steven J. Sucheck
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	thioglycosides vaccine lipopolysaccharide Pseudomonas aeruginosa outer core aminooxy glycosides Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4741b9ac31b34d53b173855d8fb42637
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spelling	oai:doaj.org-article:4741b9ac31b34d53b173855d8fb426372021-11-08T04:50:51ZSynthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide2296-889X10.3389/fmolb.2021.750502https://doaj.org/article/4741b9ac31b34d53b173855d8fb426372021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.750502/fullhttps://doaj.org/toc/2296-889XPseudomonas aeruginosa is a highly prevalent gram-negative bacterium that is becoming more difficult to treat because of increasing antibiotic resistance. As chemotherapeutic treatment options diminish, there is an increased need for vaccines. However, the creation of an effective P. aeruginosa vaccine has been elusive despite intensive efforts. Thus, new paradigms for vaccine antigens should be explored to develop effective vaccines. In these studies, we have focused on the synthesis of two L-rhamnose–bearing epitopes common to glycoforms I and II of the outer core domain of Pseudomonas aeruginosa lipopolysaccharide, α-L-Rha-(1→6)-α-D-Glc-(1→4)-α-D-GalN-(Ala)-α-aminooxy (3) and α-L-Rha-(1→3)-β-D-Glc-(1→3)-α-D-GalN-(Ala)-α-aminooxy (4), respectively. The target trisaccharides were both prepared starting from a suitably protected galactosamine glycoside, followed by successive deprotection and glycosylation with suitably protected D-glucose and L-rhamnose thioglycosides. Global deprotection resulted in the formation of targets 3 and 4 in 22 and 35% yield each. Care was required to modify basic reaction conditions to avoid early deprotection of the N-oxysuccinamido group. In summary, trisaccharides related to the L-rhamnose–bearing epitopes common to glycoforms I and II of the outer core domain of Pseudomonas aeruginosa lipopolysaccharide have been prepared as their aminooxy glycosides. The latter are expected to be useful in chemoselective oxime-based bioconjugation reactions to form Pseudomonas aeruginosa vaccines.Anshupriya SiSteven J. SucheckFrontiers Media S.A.articlethioglycosidesvaccinelipopolysaccharidePseudomonas aeruginosaouter coreaminooxy glycosidesBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thioglycosides vaccine lipopolysaccharide Pseudomonas aeruginosa outer core aminooxy glycosides Biology (General) QH301-705.5
spellingShingle	thioglycosides vaccine lipopolysaccharide Pseudomonas aeruginosa outer core aminooxy glycosides Biology (General) QH301-705.5 Anshupriya Si Steven J. Sucheck Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
description	Pseudomonas aeruginosa is a highly prevalent gram-negative bacterium that is becoming more difficult to treat because of increasing antibiotic resistance. As chemotherapeutic treatment options diminish, there is an increased need for vaccines. However, the creation of an effective P. aeruginosa vaccine has been elusive despite intensive efforts. Thus, new paradigms for vaccine antigens should be explored to develop effective vaccines. In these studies, we have focused on the synthesis of two L-rhamnose–bearing epitopes common to glycoforms I and II of the outer core domain of Pseudomonas aeruginosa lipopolysaccharide, α-L-Rha-(1→6)-α-D-Glc-(1→4)-α-D-GalN-(Ala)-α-aminooxy (3) and α-L-Rha-(1→3)-β-D-Glc-(1→3)-α-D-GalN-(Ala)-α-aminooxy (4), respectively. The target trisaccharides were both prepared starting from a suitably protected galactosamine glycoside, followed by successive deprotection and glycosylation with suitably protected D-glucose and L-rhamnose thioglycosides. Global deprotection resulted in the formation of targets 3 and 4 in 22 and 35% yield each. Care was required to modify basic reaction conditions to avoid early deprotection of the N-oxysuccinamido group. In summary, trisaccharides related to the L-rhamnose–bearing epitopes common to glycoforms I and II of the outer core domain of Pseudomonas aeruginosa lipopolysaccharide have been prepared as their aminooxy glycosides. The latter are expected to be useful in chemoselective oxime-based bioconjugation reactions to form Pseudomonas aeruginosa vaccines.
format	article
author	Anshupriya Si Steven J. Sucheck
author_facet	Anshupriya Si Steven J. Sucheck
author_sort	Anshupriya Si
title	Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
title_short	Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
title_full	Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
title_fullStr	Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
title_full_unstemmed	Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide
title_sort	synthesis of aminooxy glycoside derivatives of the outer core domain of pseudomonas aeruginosa lipopolysaccharide
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4741b9ac31b34d53b173855d8fb42637
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Synthesis of Aminooxy Glycoside Derivatives of the Outer Core Domain of Pseudomonas aeruginosa Lipopolysaccharide

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