Stabilizing Effect of Propionic Acid Derivative of Anthraquinone–Polyamine Conjugate Incorporated into α–β Chimeric Oligonucleotides on the Alternate-Stranded Triple Helix

• Published in: Bioconjugate chemistry 2011-06, Vol.22 (6), p.1039-1045
• Main Authors: Moriguchi, Tomohisa, Azam, A. T. M. Zafrul, Shinozuka, Kazuo
• Format: Article
• Language: English
• Subjects: Anthraquinones - chemistry; Anthraquinones - pharmacology; DNA - chemistry; Hydrogen-Ion Concentration; Molecular Conformation - drug effects; Molecular Structure; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Oligonucleotides - isolation & purification; Polyamines - chemistry; Polyamines - pharmacology; Propionates - chemistry; Stereoisomerism; Thermodynamics
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc100446w

Two types of anthraquinone conjugates were synthesized as non-nucleosidic oligonucleotide components. These include an anthraquinone derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid and an anthraquinone–polyamine derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid. The conjugates were successfully incorporated into the “linking-region” of the α–β chimeric oligonucleotides via phosphoramidite method as non-nucleosidic backbone units. The resultant novel α–β chimeric oligonucleotides possessed two diastereomers that were generated by the introduction of the anthraquinone conjugate with a stereogenic carbon atom. The isomers were successfully separated by a reversed-phase HPLC. UV-melting experiments revealed that both stereoisomers formed a substantially stable alternate-strand triple helix, irrespective of the stereochemistry of the incorporated non-nucleosidic backbone unit. However, the enhancing effect on thermal stability depended on the length of the alkyl linker connecting anthraquinone moiety and the propionic acid moiety. The sequence discrimination ability of the chimeric oligonucleotides toward mismatch target duplex was also examined. The T m values of the triplexes containing the mismatch target were substantially lower than the T m values of those containing the full-match target. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) required for the dissociation of the triplexes into the third strand and target duplex were also measured.