title: TEMPO-mediated glycoconjugation: a scheme for the controlled synthesis of polysaccharide conjugates.
abstract: A method for the controlled conjugation of polysaccharides (PSs) to carrier proteins based on the stoichiometric oxidation of PSs with 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) is described. In this scheme, a PS can be stoichiometrically activated, by the formation of minimal amounts of carboxylic acids with TEMPO, and subsequently coupled to a carrier protein through amide bond formation. Our exploratory studies included a number of readily available glucans, which were oxidized with several combinations of TEMPO-sodium hypochlorite preparations followed by conjugation to BSA. Following these investigations, more structurally complex bacterial capsular PSs were stoichiometrically oxidized with TEMPO-sodium hypochlorite and conjugated to BSA. Hypochlorite was deemed to be the reaction component responsible for the extent of oxidation. Collectively, the data showed this approach to be effective in designing PS-conjugates with no disruption to the structural integrity and immunochemical properties of the PS, and thus has the potential to become a reliable method for glycoconjugate vaccine synthesis.
authors.affiliation: Department of Chemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Zuchao
authors.initials: Z
authors.lastname: Ma
authors.forename: Lisa
authors.initials: L
authors.lastname: Bertolo
authors.forename: Sharif
authors.initials: S
authors.lastname: Arar
authors.forename: Mario A
authors.initials: MA
authors.lastname: Monteiro
mesh_terms: D003497:Cyclic N-Oxides / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000737:chemistry*
chemical_list: D003497:Cyclic N-Oxides; D005936:Glucans; D006001:Glycoconjugates; D011135:Polysaccharides, Bacterial; D011506:Proteins; D018074:Vaccines, Conjugate; D012710:Serum Albumin, Bovine; C001290:glucan nigeran; C003959:TEMPO