A simple, convenient method to synthesize cobalamins: synthesis of homocysteinylcobalamin, N-acetylcysteinylcobalamin, 2-N-acetylamino-2-carbomethoxyethanethiolatocobalamin, sulfitocobalamin and nitrocobalamin.
Glutathionylcobalamin, nitrocobalamin and sulfitocobalamin are important cobalamin metabolites isolable from human tissues. Herein we demonstrate that a procedure used to synthesize and isolate gamma-glutamylcysteinylcobalamin and glutathionylcobalamin in aqueous solution in high yield and purity can be used to synthesize other novel, biologically relevant thiolatocobalamins, including d,l-homocysteinylcobalamin, N-acetyl-l-cysteinylcobalamin (Na(+) salt) and 2-N-acetylamino-2-carbomethoxy-l-ethanethiolatocobalamin, as well as other non-alkylcobalamins, such as sulfitocobalamin (Na(+) salt) and nitrocobalamin. This uncomplicated, general procedure will assist researchers in identifying unknown cobalamin metabolites isolated from biological samples, and researchers interested in studying the uptake and intracellular cobalamin processing mechanisms utilizing non-alkylcobalamin derivatives that are not yet commercially available. The X-ray structure and XAS spectrum of N-acetyl-l-cysteinylcobalamin are also presented.
Suarez-Moreira
Edward
E
School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA.
Hannibal
Luciana
L
Smith
Clyde A
CA
Chavez
Roberto A
RA
Jacobsen
Donald W
DW
Brasch
Nicola E
NE
D018360:Crystallography, X-Ray; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
C516436:2-N-acetylamino-2-carbomethoxyethanethiolatocobalamin; C516435:N-acetylcysteinylcobalamin; C516434:homocysteinylcobalamin; D006710:Homocysteine; C016763:sulfitocobalamin; C092105:nitritocobalamin; D003545:Cysteine; D014805:Vitamin B 12