Chemoenzymatic n.c.a synthesis of the coenzyme UDP-2-deoxy-2-(~(18)F)fluoro-alpha-D-glucopyranose as substrate of glycosyltransferases

摘要

The development of ~(18)F-labelling methods adopted to proteins and bioactive peptides is of great interest in radiopharmaceutical sciences. In order to provide ~(18)F-labelled sugars as a polar prosthetic group for an enzymatic ~(18)F-labelling procedure, an appropriate nucleotide activated sugar is needed. Here, we present the radiosynthesis of n.c.a. UDP-2-deoxy-2-[~(18)F]fluoro-alpha-D-glucopyranose (UDP-[~(18)F]FDG) as a substrate for glycosyltransferases. The MacDonald synthesis of [~(18)F]FDG-1-phosphate was successfully combined with an enzymatic activation to obtain UDP-[~(18)F]FDG directly in an aqueous medium located in the void volume of a solid phase cartridge. The radiochemical yield of UDP-[~(18)F]FDG was 20% (based on [~(18)F]fluoride) after a total synthesis time of 110 min. Thus, an intermediate was provided for the enzymatic transfer of [~(18)F]FDG using UDP-[~(18)F]FDG as glycosyl donor making use of a suitable glycosyltransferase. This would represent a highly selective and mild ~(18)F-labelling method for glycosylated biomolecules.