Oligodeoxynucleotide analogs with 5′‐linked anthraquinone

Abstract

We report here the synthesis of novel 5'-linked oligodeoxynucleotides, both normal phosphodiester and phosphorothioate analogs, in which a covalently attached group at the Y-terminus is an anthraquinone. These compounds represent a new class of antisense compounds in which the base sequence of the oligodeoxynucleotide serves to deliver a nuclease-resistant reactive drug-like molecule to a cellular target nucleic acid (mRNA or DNA).

Long-distance charge transport in duplex DNA: The phonon-assisted polaron-like hopping mechanism

“…Duplexes were prepared by PCR using 19-mer primers and DNA(2) as the template (37). PCR reactions contained 0.2 mM dNTPs, 10 mM Tris⅐HCl (pH 9.0), 50 mM KCl, 0.1% Trition X-100, 1 mM MgCl 2 , 10% DMSO, and 2.5 units of Taq polymerase per 100 l reaction.…”

Synthesis and Duplex-Forming Property of Oligonucleotides Bearing a Novel Polyamine-Modified Intercalator at the Terminal or the Internal Position

“…(7). 1-(6-hydroxyhexylamino)anthraquinone [15] (6) (120 mg, 0.37 mmol) and N,N-diisopropylethylamine (0.12 ml, 0.74 mmol) were dissolved in dry CH 2 Cl 2 (3 ml), and to this solution was added 2-cyanoethyl N,N-diisopropyl phosphorochloridite (0.12 ml, 0.56 mmol) at 0 • C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with CH 2 Cl 2 , washed twice with 5% NaHCO 3 aq and once with brine, and the organic layer was dried over Na 2 SO 4 , filtered, and concentrated to dryness. The residue was purified by silica gel column chromatography (CH 2 Cl 2 :ethyl acetate:triethylamine = 45:45:10, (v/v/v)) to give the desired compound 7 (107 mg, 55%) as a dark red solid.…”

“…It should be noted that the phosphoramidite 5 is somewhat unstable under storage; therefore, it was used immediately after the purification with silica-gel column chromatography. For the synthesis of ODN-2, nonpolyamine conjugated anthraquinone derivative [15] (6) was also converted to the corresponding phosphoramidite derivative (7) in the usual manner. The incorporation of 5 and 7 into oligonucleotide were carried out the same as the incorporation of normal nucleoside phosphoramidites.…”

Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate

“…Numerous past reports have characterized the strong tendency for anthraquinone derivatives to intercalate into duplex DNA (see for example [16][17][18][19][20][21][22][23][24][25][26][27] and therefore a similar interaction was expected for the duplexes formed by the dimethylanthraquinone-oligodeoxynucleotide conjugate and its complementary target. This non-covalent binding was characterized by an increase in the thermal melting temperature (T m ) of duplex DNA in the presence of the quinone (Table 1).…”

“…Numerous bis(aminoalkyl) anthraquinones have also been prepared as anticancer agents based on their strength as intercalators (17)(18)(19) and this binding property has since been used to promote platinum-DNA reaction through construction of anthraquinone-cisplatin conjugates (20). Anthraquinone derivatives have similarly been coupled to antisense and antigene reagents in order to strengthen their association with target DNA, as well as to enhance their cellular uptake and decrease their sensitivity to nucleases (21)(22)(23)(24)(25)(26)(27).…”