Monitoring the Intracellular Metabolism of Nucleoside Phosphoramidate Pronucleotides by ³¹P NMR

The intracellular metabolism of 3′-azido-3′-deoxythymidine (AZT)-(L)-tryptophan methyl ester phosphoramidate (L-ATO) and AZT-(L)-phenylalanine methyl ester phosphoramidate (L-APO) by the human T-lymphoblastoid cell line CCRF-CEM (CEM-1.3) and peripheral blood mononuclear cell line (PBMC) was investigated with high field ³¹P NMR spectroscopy. The AZT amino acid phosphoramidates were shown to accumulate intracellularly and to be readily converted into AZT-MP by both tissues types. Thus, the efficient delivery of nucleoside monophosphates to cells can be facilitated by nucleoside phosphoramidate pronucleotides.