Conjugation of Streptococcal Capsular Saccharides

摘要

Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive amination of oxidized sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

主权项

1. A process for preparing a conjugate of an S. agalactiae capsular saccharide and a carrier molecule, comprising the steps of: (a) oxidizing an S. agalactiae capsular saccharide in order to introduce an aldehyde group into at least one terminal sialic acid residue in the saccharide; (b) subjecting the aldehyde group to reductive amination with ammonia or a primary amine, to give a —CH2-linked amine; (c) reacting the —CH2-linked amine with a bifunctional linker, to give an activated saccharide; and (d) reacting the activated saccharide with a carrier molecule, thereby giving the conjugate.