title: Dialdehydes lead to exceptionally fast bioconjugations at neutral pH by virtue of a cyclic intermediate.
abstract: One of the open challenges in chemical biology is to identify reactions that proceed with large rate constants at neutral pH values. As shown here, dialdehydes react with O-alkylhydroxylamines at rates of 500 M(-1) s(-1) at neutral pH values in the absence of catalysts. The key to these conjugations is an unusually stable cyclic intermediate, which ultimately undergoes dehydration to yield an oxime. The scope and limitations of the method are outlined, as well as its application in bioconjugation and a mechanistic interpretation that will facilitate further developments of reactions with alkylhydroxylamines at low substrate concentrations.
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland).
authors.forename: Pascal
authors.initials: P
authors.lastname: Schmidt
authors.forename: Linna
authors.initials: L
authors.lastname: Zhou
authors.forename: Kiril
authors.initials: K
authors.lastname: Tishinov
authors.forename: Kaspar
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Dennis
authors.initials: D
authors.lastname: Gillingham
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D002384:Catalysis; D004247:DNA / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006898:Hydroxylamines / Q000737:chemistry*; D007700:Kinetics; D010091:Oximes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000596:Amino Acids; D006898:Hydroxylamines; D010091:Oximes; D010455:Peptides; D004247:DNA
keywords: aldehydes; bioconjugation; hydroxylamines; kinetics; oximes