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Biomedical subjects

F Morvan

Publications and source records attributed to F Morvan.

64 records · Page 4Linked to original sources
PubMedDate not supplied

Triple, MPEG-conjugated, helix-forming oligonucleotides (TRIPEGXs): liquid-phase synthesis of natural and chimeric "all-purine" sequences linked to high molecular weight poly(ethylene glycols).

Long "all-purine" oligonucleotides, up to the 20mer, known to be active as antigene effectors, conjugated to high molecular weight monomethoxy poly(ethylene glycol)s (MPEG)s, were successfully synthesized. Through a liquid-phase, MPEG-supported process, both natural and chimeric sequences containing selected phosphorothioate backbone modifications were obtained, purified, and characterized. To follow their cellular trafficking, a fluorescent probe was linked by soluble supported organic reactions to the 5'-terminus, and the efficiency of the different synthetic procedures for the introduction of a fluorescein moiety was compared. The usefulness of the fluorescent marker was estimated by laser confocal microscopy that ascertains that the MPEG-conjugation enhances the oligonucleotide capacity to cross the cellular membranes and to be accumulated inside the nuclei.

Cell Membrane Permeability↗
PubMedDate not supplied

Prooligonucleotides exhibit less serum-protein binding than phosphodiester and phosphorothioate oligonucleotides.

The protein-binding properties of dodecathymidine derivatives (prooligos) bearing either methyl- or tert-butyl-S-acylthioethyl (Me- or tBuSATE) protecting groups were evaluated. The dissociation constants (Kd) were estimated for complexes of prooligos with serum blood proteins and lactoferrin using prooligos to compete the binding of the radiolabeled, alkylating probe oligonucleotide CIRp(T)12 with the proteins. tBuSATE and MeSATE prooligos have decreased affinity of binding with serum proteins and lactoferrin compared with their parent oligos. These data suggest that prooligos should cause less side effects which combined with their stability to nucleases and enhanced permeability into cells make them potentially useful for design of therapeutics.

Animals↗
PubMedDate not supplied

Polyimidazole conjugated oligonucleotides reach the nucleus of HeLa cells.

Oligonucleotide models bearing 6, 12 or 18 histamine residues were synthesized on solid support and labeled with fluorescein. Only the oligo with 6 histamine residues showed a high uptake in HeLa cells with a nuclear localization. Experiment a 4 degrees C or with bafilomicyn A1 suggest that uptake proceeded by an endocytosis mechanism followed by a destabilization of the membrane. Once in the cytoplasm the oligo reached rapidly the nucleus.

Anti-Bacterial 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↗