Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.
The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF MS. This technique allows a facile identification and a relative quantification of metabolites produced. We showed that the relative peak intensities were similar to the relative metabolite proportions that permitted the determination of their half-lives. We found a good fit between the calculated kinetics curves and the experimental points. The oligonucleotide prodrug was fully metabolized to yield the dodecathymidine phosphorothioate likely through a carboxyesterase mediated mechanism.
Brès
J C
JC
Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR 5625 CNRS-UM II, Université Montpellier II, France.
Morvan
F
F
Lefebvre
I
I
Vasseur
J J
JJ
Pompon
A
A
Imbach
J L
JL
D001711:Biotransformation; D002457:Cell Extracts; D009841:Oligonucleotides / Q000737:chemistry / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013936:Thymidine / Q000737:chemistry
D002457:Cell Extracts; D009841:Oligonucleotides; D011355:Prodrugs; D013936:Thymidine