title: Stability studies of hydrazide and hydroxylamine-based glycoconjugates in aqueous solution.
abstract: Glycoconjugates can be readily formed by the condensation of a free-reducing terminus and a strong alpha-effect nucleophile, such as a hydrazide or a hydroxylamine. Further characterization of a series of glycoconjugates formed from xylose, glucose and N-acetylglucosamine, and either p-toluenesulfonyl hydrazide or an N-methylhydroxylamine, was carried out to gain insight into the optimal conditions for the formation of these useful conjugates, and their stability. Their apparent association constants (9-74 M(-1)) at pH 4.5; as well, as rate constants for hydrolysis, at pH 4.0, 5.0 and 6.0 (37 degrees C), were determined. The half-lives of the conjugates varied between 3h and 300 days. All the compounds were increasingly stable as the pH approached neutrality. Conjugate hydrolysis rates mirrored those found for O-glycoside hydrolysis where conjugates formed from electron-rich monosaccharides hydrolyzed more rapidly.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, Canada.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Gudmundsdottir
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Paul
authors.forename: Mark
authors.initials: M
authors.lastname: Nitz
mesh_terms: D002240:Carbohydrate Sequence; D004355:Drug Stability; D006001:Glycoconjugates / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006898:Hydroxylamines / Q000737:chemistry*; D015394:Molecular Structure; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D006001:Glycoconjugates; D006834:Hydrazines; D006898:Hydroxylamines; D012996:Solutions; D014867:Water