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)

• Published in: Bioconjugate chemistry Vol. 12; no. 5; pp. 719 - 725
• Main Authors: Ballico, M, Drioli, S, Morvan, F, Xodo, L, Bonora, G. M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.09.2001
• Subjects: Cell Membrane Permeability; DNA; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Fluorescein; Fluorescent Dyes; Humans; K562 Cells; Microscopy, Confocal; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - pharmacokinetics; Phosphates; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - pharmacokinetics; Purines - chemistry; Thionucleotides
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc010034b

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.