title: Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
abstract: 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. The oligonucleotide prodrug was fully metabolized to yield the T12 phosphorothioate likely through a carboxyesterase mediated mechanism.
authors.affiliation: Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR 5625 CNRS-UM II, Université Montpellier II, Place E. Bataillon, 34095 Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Morvan
authors.forename: J C
authors.initials: JC
authors.lastname: Brès
authors.forename: I
authors.initials: I
authors.lastname: Lefebvre
authors.forename: J J
authors.initials: JJ
authors.lastname: Vasseur
authors.forename: A
authors.initials: A
authors.lastname: Pompon
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
mesh_terms: D001711:Biotransformation; D009841:Oligonucleotides / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D011742:Pyrimidine Nucleotides / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013936:Thymidine / Q000031:analogs & derivatives*
chemical_list: D009841:Oligonucleotides; D011355:Prodrugs; D011742:Pyrimidine Nucleotides; D013936:Thymidine