RESUMEN
We report the synthesis and self-assembly of two lipophilic 2'-deoxyguanosine (G) derivatives whose fluorescence intensity is modulated by self-assembly into supramolecular G-quadruplexes (SGQs). Whereas both derivatives self-assemble isostructurally, one shows up to 100% emission enhancement while the other shows an initial enhancement, followed by 10% quenching. Thus, the rotational restrictions resulting from self-assembly are enough to induce significant changes in emission, but it is critical to consider the specific interactions between fluorophores since they will determine the ultimate emission signature. These findings could open the door to the development of luminescent supramolecular sensors and probes.
Asunto(s)
Desoxiguanosina/síntesis química , G-Cuádruplex , Desoxiguanosina/análogos & derivados , Desoxiguanosina/química , Fluorescencia , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/química , Modelos Moleculares , Estructura MolecularRESUMEN
The free nucleoside 2'-deoxyguanosine (dGuo) is the most susceptible to oxidation by reactive oxygen species (ROS) compared to the other free nucleosides, and its oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) has been used as a biomarker to quantify oxidative stress damage. We investigated different reactions using Fe(2+) or Cu(2+) and H2O2 in order to identify the reaction with the best yield. HPLC coupled with a UV detector and micrOTOF mass spectrometry were used to detect and confirm the identity of 8-oxodGuo. The optimized reaction synthesized 8-oxodGuo with a yield of 72.0%, much higher than that previously described in the literature. Our improved method for 8-oxodGuo synthesis could be extremely useful for assays that require the synthesis of internal standards labeled with stable isotopes.
Asunto(s)
Ácido Ascórbico/química , Cobre/química , Desoxiguanosina/análogos & derivados , Desoxiguanosina/química , Peróxido de Hidrógeno/química , 8-Hidroxi-2'-Desoxicoguanosina , Cromatografía Líquida de Alta Presión , Desoxiguanosina/síntesis química , Desoxiguanosina/aislamiento & purificación , Hierro/química , Espectrometría de Masas , Metales/química , Espectrofotometría UltravioletaRESUMEN
The reaction of 2'-deoxyguanosine with the alpha,beta-unsaturated aldehydes trans-2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and trans,trans-2,4-decadienal in THF gives rise to three novel adducts: 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-3,5-dihydro-imidazo[1,2-a]purin-9-one-7-yl)-propyl]-3,5-dihydro-imidazo[1,2-a]purin-9-one (A7) and 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-(tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-a]purin-9-one (A8 and A9), which are not observed in the absence of THF. These adducts were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adduct A7 consists of two 1,N2-etheno-2'-deoxyguanosine (1,N2-epsilon dGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N2-epsilon dGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N2-epsilon dGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N2-epsilon dGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N2-epsilon dGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.