National Research Council of Canada

University of Ottawa

University of Massachusetts

Ian C Schoenhofen

Dennis M Whitfield

Susan M Logan

Christopher Noyce Boddy

Benjamin R Lundgren

Sanjay Ram

Dennis Whitfield

Andrew Cox

James C Richards

Frank St Michael

Dhamodharan Neelamegan

Susan Logan

has become resistant to almost every conventional antibiotic. Described herein is the use of CMP-nonulosonate analogues to counter gonococcal complement evasion. The nonulosonate sugar is incorporated into the lipooligosaccharide of thewhich in turn reduces the serum resistance of the bacteria. This provides a novel therapeutic strategy against the global threat of multi-drug resistant gonorrhea.

therapeutic based on CMP-nonulosonate sugars

The present invention relates to the cell-based production of bacterial nonulosonates and their biosynthetic precursors. Specifically, the present invention provides recombinant cells for the production of pseudaminic acid, legionaminic acid, UDP-2,4-diacetamido-2,4,6-trideoxy-&#x3b2;-L-altropyranose, and UDP-2,4-diacetamido-2,4,6-trideoxy-&#x3b1;-D-glucopyranose. Methods for producing the sugars are also provided.

Cell-based production of nonulosonates

has become resistant to almost every conventional antibiotic. Described herein is the use of CMP-nonulosonate analogs to counter gonococcal complement evasion. The nonulosonate sugar is incorporated into the lipooligosaccharide of thewhich in turn reduces the serum resistance of the bacteria. This provides a novel therapeutic strategy against the global threat of multi-drug resistant

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The present invention relates to the cell-based production of bacterial nonulosonates and their biosynthetic precursors. Specifically, the present invention provides recombinant cells for the production of pseudaminic acid, legionaminic acid, UDP-2,4-diacetamido-2,4,6-trideoxy-&#x25a1;-L-altropyranose, and UDP-2,4-diacetamido-2,4,6-trideoxy-&#x25a1;-D-glucopyranose. Methods for producing the sugars are also provided.

The sialic acid-like sugar legionaminic acid is found as a virulence-associated surface glyco-conjugate inand. In this work, we have purified and biochemically characterized eleven candidate biosynthetic enzymes from, thereby fully reconstituting the biosynthesis of legionaminic acid and its CMP-activated form, starting from fructose-6-P. This pathway involves unique GDP-linked intermediates and provides a facile means for the efficient large-scale synthesis of an important sialic acid mimic and novel precursors.

Biosynthesis of CMP-legionaminic acid from fructose-6-P, and respective pathway intermediates, using novel GDP-linked precursors

Novel enzymes, processes and antigenic structures useful in producing vaccines and compounds useful in combating gram-negative bacteria are described. Enzymes were isolated from the slime moldand used to specifically degrade lipopolysaccharide (LPS). Enzymatic degradation permits residues of the LPS molecule, including immunogenic epitopes of the core oligosaccharide portion of the LPS, to remain unmodified during this enzymatic removal of fatty acids from the lipid A region of the LPS molecule.

Enzymatic degradation of lipid A fatty acids of bacterial LPS

The present invention describes compounds of Formula I or a pharmaceutically acceptable salts or derivatives thereof. Compositions comprising compounds of Formula I are also described. The present invention further relates to a method of producing non-2-enonate compounds. 

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Ottawa, Canada

Ian C Schoenhofen