Preparation, properties and biological activities of succinyl derivatives of vitamin B12.
Three new derivatives of vitamin B12,0-2'-succinyl-, 0-5'-succinyl-, and 0-2', 0-5'-disuccinyl-vitamin B12, whose alpha-ribose moieties of the nucleotide ligand are succinylated, were prepared by reaction of the vitamin with succinic anhydride. The first succinylation took place rapidly and almost predominantly on 5'-OH of alpha-ribose, and the second succinylation much more slowly on 2'-OH. From the behaviors in paper electrophoresis and the lability to CH- of cobalt-base bond of 0-2'-succinylated vitamin B12 derivatives, it was suggested that the terminal COOH of the 0-2'-succinyl group forms an inner salt with the imidazole nucleus of 5,6-dimethylbenzimidazole. Monosuccinyland disuccinyl-vitamin B12 by mild acid or base hydrolysis. Heating at 130 degrees for 5 min also led to the complete severance of the succinyl group of 0-5'-succinyl-vitamin B12. None of the three succinly derivatives inhibited the diol dehydrase reaction when added with coenzyme B12, SUggesting that the ability to bind to the apoenzyme is strongly diminished or almost lost by succinylation on 2'- or 5'-OH of alpha-ribose. None of the succinyl vitamin B12 compounds showed either biological activity or anti-vitamin B12 activity when tested with Escherichia coli 215, a methionine-B12 auxotroph. None of them significantly inhibited [3-H] vitamin B12 uptake by E. coli 215 cells. This observation implies that succinyl derivatives of vitamin B12 are hardly incorporated into the cells of E. coli.
D001692:Biological Transport; D002855:Chromatography, Thin Layer; D004590:Electrophoresis, Paper; D004754:Enterobacter / Q000201:enzymology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors; D007700:Kinetics; D011409:Propylene Glycols; D012266:Ribose; D013329:Structure-Activity Relationship; D013386:Succinates; D013997:Time Factors; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D011409:Propylene Glycols; D013386:Succinates; D012266:Ribose; D006836:Hydro-Lyases; D014805:Vitamin B 12