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Biomedical subjects

I Lefebvre

Publications and source records attributed to I Lefebvre.

36 records · Page 2Linked to original sources
PubMed1992

"On-line internal surface reversed-phase cleaning": the direct HPLC analysis of crude biological samples. Application to the kinetics of degradation of oligonucleotides in cell culture medium.

An "on-line" HPLC analysis of crude biological samples is described. A precolumn of internal surface reversed-phase material allows the passage of proteins and other unwanted products while retaining analytes which are transferred, concentrated and chromatographed on a conventional reverse-phase or ion-exchange HPLC column. This protocol allows precise kinetics of the degradation of an oligonucleotide in cell culture to be obtained without radiolabeling or sample preparation.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Anti-human immunodeficiency virus type 1 activities of dideoxynucleoside phosphotriester derivatives in primary monocytes/macrophages.

Mononucleoside phosphotriester derivatives of dideoxynucleosides, following intracellular enzymatic activation, are likely to liberate their parent 5'-nucleoside monophosphate. Prodrugs of 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'- dideoxythymidine (d4T), 2',3'-dideoxyinosine (ddl) and 2',3'-dideoxyadenosine (ddA) were evaluated for their anti-HIV1 activities in monocyte-derived macrophages, cells which are known to have low levels of nucleoside kinases. Prodrugs were found to be much more active, or just as active, as the corresponding dideoxynucleoside. Furthermore, their selectivity index was enhanced by a factor of 2 to 200.

Antiviral Agents↗
PubMedDate not supplied

Design of new mononucleotide prodrugs: aryl (SATE) phosphotriester derivatives.

Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.

Anti-HIV Agents↗
PubMedDate not supplied

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. The oligonucleotide prodrug was fully metabolized to yield the T12 phosphorothioate likely through a carboxyesterase mediated mechanism.

Biotransformation↗
PubMedDate not supplied

SATE (aryl) phosphotriester series. II. Stability studies and physicochemical parameters.

The stability of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-pivaloyl-2-thioethyl (tBuSATE) group and various aryl residues derived from L-tyrosine was evaluated in biological media. The results demonstrate that such compounds give rise to intracellular delivery of the parent mononucleotide through esterase and phosphodiesterase hydrolytic steps, successively.

Cell Line↗