Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d2)

The chemical synthesis of the dideuterium-labelled ATP analogue 1-adenosin-5'-yl-3-(3-methylbut-3-en-1,1-d2-1-ol) triphosphoric acid diester (ApppI(d2)) is described. ApppI has been reported to be an important mevalonate pathway metabolite, induced by nitrogen-containing bisphosphonates used for the treatment of several diseases related to the calcium metabolism, of which osteo-porosis is the most well-known. The availability of ApppI(d2) opens possibilities to quantitative measurements of ApppI in biologi-cal samples by mass spectrometry. The synthesized target compound ApppI(d2) was purified by high-performance counter current chromatography and characterized by 1H, 13C, and 31P NMR spectroscopy as well as high-resolution mass spectrometry.

Automated summary

The chemical synthesis of the dideuterium-labelled ATP analogue ApppI(d2) is described, and its purification and characterization by various techniques are reported. The quantitative measurement of ApppI in biological samples is of great importance for the study of related diseases.