Rhamnose-polysaccharides
AssigneeUniversity of Dundee
InventorHELGE DORFMUELLER
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Abstract
The present invention relates to a method of synthesizing a rhamnose polysaccharide. The invention also relates to a synthetic streptococcal polysaccharide, a streptococcal glycoconjugate, an immunogenic composition or vaccine comprising the streptococcal polysaccharide or glycoconjugate and the polysaccharide, glycoconjugate, immunogenic composition or vaccine for use in raising an immune response in an animal or for use in treating or preventing a disease, condition or infection with a streptococcal aetiology.
Claims37
A method of synthesizing a rhamnose polysaccharide, the method comprising
- (i) transferring a rhamnose moiety to a hexose monosaccharide, disaccharide or trisaccharide using a hexose-β-1,4-rhamnosyltransferase, a hexose-α-1,2-rhamnosyltransferase and/or a hexose-α-1,3-rhamnosyltransferase, or an enzymatically active fragment or variant thereof to form a disaccharide, trisaccharide or tetrasaccharide comprising a rhamnose moiety at a non-reducing end of the disaccharide, trisaccharide or tetrasaccharide;
- (ii) generating the rhamnose polysaccharide by extending from the rhamnose moiety at the non-reducing end of the disaccharide, trisaccharide or tetrasaccharide using a heterologous bacterial enzyme Streptococcus pyogenes Group A carbohydrate enzyme C (GacC) and/or Streptococcus pyogenes Group A carbohydrate enzyme G (GacG) or an enzymatically active homologue, variant or fragment thereof.
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A synthetic streptococcal polysaccharide, the polysaccharide having a non-reducing end comprising a linear chain of rhamnose moieties and a reducing end comprising a hexose monosaccharide, disaccharide, or trisaccharide, wherein the polysaccharide comprises a α-1,3 bond or a α-1,2 bond between the hexose monosaccharide, disaccharide, or trisaccharide and the linear chain of rhamnose moieties;
- or the polysaccharide comprises a β-1,4 bond between the hexose monosaccharide, disaccharide, or trisaccharide and the linear chain of rhamnose moieties and the hexose monosaccharide, disaccharide, or trisaccharide does not comprise N-acetylglucosamine.
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A bacterial host cell, the bacterial host cell comprising a hexose-β-1,4-rhamnosyltransferase, a hexose-α-1,2-rhamnosyltransferase or a hexose-α-1,3-rhamnosyltransferase, or an enzymatically active fragment or variant thereof and a heterologous bacterial enzyme GacC and/or GacG or an enzymatically active homologue, variant or fragment thereof.
A kit of parts, the kit comprising:
- (i) a nucleic acid sequence encoding a hexose-β-1,4-rhamnosyltransferase, a hexose-α-1,2-rhamnosyltransferase or a hexose-α-1,3-rhamnosyltransferase, or an enzymatically active fragment or variant thereof;
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- (ii) a nucleic acid sequence encoding a heterologous bacterial enzyme GacC and/or GacG or an enzymatically active homologue, variant, or fragment thereof.
Dependencies are inferred from the claim text.