Two new phosphoramidite building blocks for DNA synthesis were synthesized from 1,5- and 2,6-dihydroxyanthraquinones via alkylation with 3-bromo-1-propanol followed by DMT-protection. The novel synthesized 1,5-, and 2,6-disubstituted anthraquinone monomers H₁₅ and H₂₆ are incorporated into a G-quadruplex by single and double replacements of TGT and TT loops. Monomers H₁₅ and H₂₆ were found to destabilize G- quadruplex structures for all single replacements of TGT or TT loops. The largest destabilization is observed when H₂₆ linker is replacing a TT loop. On the contrary, the presence of anthraquinone monomers in two TT loops led to 1-18 °C increase in their thermal stabilities depending on linker attachment geometry of the monomers. The presence of H₁₅ and H₂₆ linkers replacing two TT loops results in the highest stabilization of the G-quadruplex structure by 18.2 °C. Circular dichroism spectroscopy of all anthraquinone-modified quadruplexes revealed no change of the anti-parallel structure when compared to the wild type under potassium buffer conditions. The significantly increased thermostabilities were interpreted by molecular modeling of anthraquinone-modified G-quadruplexes.
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