Oligonucleotides conjugated with short chemically defined polyethylene glycol chains are efficient antisense agents.
Bottom Line: On the other hand, the attachment of long PEG chains negatively influences the pharmacodynamic effect by reducing the hybridization efficiency.Circular dichroism showed that the tethering of PEG12-chains to phosphodiester and phosphorothioate oligonucleotides had no influence on their secondary structure and did not reduce the affinity to the counter strand.In an in vitro tumor model, a luciferase reporter assay indicated unchanged gene silencing activity compared to unmodified compounds, and even slightly superior target down regulation was found after treatment with a phosphorothioate modified conjugate.
Affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstraße 14, 1090 Vienna, Austria.Show MeSH
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Mentions: Circular dichroism spectra were recorded to detect a possible influence of the ligands on the structural properties of the paired oligonucleotide duplexes. Neither 3′- nor 5′-attachment changed the curve shape (Fig. 1). The slightly higher band intensities even indicate a small stabilization of the duplex structure caused by the PEGylation. Similar results were found for the phosphorothioate oligonucleotides 4 and 5 (data not shown).
Affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstraße 14, 1090 Vienna, Austria.