Synthesis and biological activity of a profluorescent analogue of coenzyme B12.
We describe here the synthesis and chemical properties of linear(lin)-benzoadenosylcobalamin, a coenzyme B12 analogue that has a laterally extended nucleoside in the upper axial position. It is an effective competitive inhibitor of ribonucleotide reductase from Lactobacillus leichmannii. lin-Benzoadenosylcobalamin is nonfluorescent in solution but, on homolytic (light) or heterolytic (acid, cyanide) cleavage of the carbon-cobalt bond, forms fluorescent products. In addition, fluorescence is detectable on binding of the coenzyme analogue to ribonucleotide reductase, and the observed fluorescence polarization of the lin-benzoadenosyl moiety indicates that it is bound loosely to the enzyme when the coenzyme is partially dissociated.
D007778:Lactobacillus / Q000201:enzymology; D011485:Protein Binding; D012264:Ribonucleotide Reductases / Q000378:metabolism; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D012264:Ribonucleotide Reductases; D014805:Vitamin B 12