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Synthesis and Molecular Modeling of Thermally Stable DNA G‐Quadruplexes with Anthraquinone Insertions
Author(s) -
Gouda Alaa S.,
Amine Mahasen S.,
Pedersen Erik B.
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700065
Subject(s) - chemistry , anthraquinone , g quadruplex , dna , stereochemistry , molecular model , organic chemistry , biochemistry
Two new phosphoramidite building blocks for DNA synthesis were synthesized from 1,5‐ and 2,6‐dihydroxyanthraquinones through alkylation with 3‐bromo‐1‐propanol followed by DMT‐protection. The novel synthesized 1,5‐ and 2,6‐disubstituted anthraquinone monomers H 15 and H 26 are incorporated into a G‐quadruplex by single and double replacements of TGT and TT loops. Monomers H 15 and H 26 were found to destabilize G‐quadruplex structures for all single replacements of TGT or TT loops. The largest destabilization was observed when H 26 linker replaced a TT loop. In contrast, 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 H 15 and H 26 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 antiparallel structure when compared with the wild type under potassium buffer conditions. The significantly increased thermostabilities were interpreted by molecular modeling of anthraquinone‐modified G‐quadruplexes.