title: A blue corrinoid from partial degradation of vitamin B12 in aqueous bicarbonate: spectra, structure, and interaction with proteins of B12 transport.
abstract: Cobalamin (Cbl) is a complex cofactor produced only by bacteria but used by all animals and humans. Cyanocobalamin (vitamin B(12), CNCbl) is one commonly isolated form of cobalamin. B(12) belongs to a large group of corrinoids, which are characterized by a distinct red color conferred by the system of conjugated double bonds of the corrin ring retaining a Co(III) ion. A unique blue Cbl derivative was produced by hydrolysis of CNCbl in a weakly alkaline aqueous solution of bicarbonate. This corrinoid was purified and isolated as dark blue crystals. Its spectroscopic analysis and X-ray crystallography revealed B-ring opening with formation of 7,8-seco-cyanocobalamin (7,8-sCNCbl). The unprecedented structural change was caused by cleavage of the peripheral C-C bond between saturated carbons 7 and 8 of the corrin macrocycle accompanied by formation of a C═C bond at C7 and a carbonyl group at C8. Additionally, the C-amide was hydrolyzed to a carboxylic acid. The extended conjugation of the π-system caused a considerable red shift of the absorbance spectrum. Formation and degradation of 7,8-sCNCbl were analyzed qualitatively. Its interaction with the proteins of mammalian Cbl transport revealed both a slow binding kinetics and a low overall affinity. The binding data were compared to those of other monocarboxylic derivatives and agreed with the earlier proposed scheme for two-step ligand recognition. The obtained results are consistent with the structural models of 7,8-sCNCbl and the transport proteins intrinsic factor and transcobalamin. Potential applications of the novel derivative for drug conjugation are discussed.
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Science Park, Gustav Wieds Vej 10, DK 8000 Aarhus C, Denmark. snf@mb.au.dk
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Fedosov
authors.forename: Markus
authors.initials: M
authors.lastname: Ruetz
authors.forename: Karl
authors.initials: K
authors.lastname: Gruber
authors.forename: Natalya U
authors.initials: NU
authors.lastname: Fedosova
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kräutler
mesh_terms: D001639:Bicarbonates / Q000737:chemistry / Q000378:metabolism*; D045728:Corrinoids / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000502:physiology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D045728:Corrinoids; D014867:Water; D014805:Vitamin B 12