Novel conjugated G-quadruplex-forming d(TG3AG) oligonucleotides, linked to hydrophobic groups through phosphodiester bonds at 50-end, have been synthesized as potential anti-HIV aptamers, via a fully automated, online phosphoramidite-based solid-phase strategy. Conjugated quadruplexes showed pronounced anti-HIV activity with some preference for HIV-1, with inhibitory activity invariably in the low micromolar range. The CD and DSC monitored thermal denaturation studies on the resulting quadruplexes, indicated the insertion of lipophilic residue at the 50-end, conferring always improved stability to the quadruplex complex (20 < DTm < 40 C). The data suggest no direct functional relationship between the thermal stability and anti-HIV activity of the folded conjugated G-quartets. It would appear that the nature of the residue at 50 end of the d(TG3AG) quadruplexes plays an important role in the thermodynamic stabilization but a minor influence on the anti-HIV activity. Moreover, a detailed CD and DSC analyses indicate a monophasic behaviour for sequences I and V, while for ODNs (II–IV) clearly show that these quadruplex structures deviate from simple two-state melting, supporting the hypothesis that intermediate states along the dissociation pathway may exist

Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG) Quadruplexes bearing hydrophobic tails at the 5'-end / Romanucci, Valeria; Milardi, D.; Campagna, T.; Gaglione, M.; Messere, Anna; D’Urso, A.; Crisafi, E.; La Rosa, C.; Zarrelli, Armando; Balzarini, J.; DI FABIO, Giovanni. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 22:3(2014), pp. 960-966. [10.1016/j.bmc.2013.12.051]

Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG) Quadruplexes bearing hydrophobic tails at the 5'-end

ROMANUCCI, VALERIA;MESSERE, ANNA;ZARRELLI, ARMANDO;DI FABIO, GIOVANNI
2014

Abstract

Novel conjugated G-quadruplex-forming d(TG3AG) oligonucleotides, linked to hydrophobic groups through phosphodiester bonds at 50-end, have been synthesized as potential anti-HIV aptamers, via a fully automated, online phosphoramidite-based solid-phase strategy. Conjugated quadruplexes showed pronounced anti-HIV activity with some preference for HIV-1, with inhibitory activity invariably in the low micromolar range. The CD and DSC monitored thermal denaturation studies on the resulting quadruplexes, indicated the insertion of lipophilic residue at the 50-end, conferring always improved stability to the quadruplex complex (20 < DTm < 40 C). The data suggest no direct functional relationship between the thermal stability and anti-HIV activity of the folded conjugated G-quartets. It would appear that the nature of the residue at 50 end of the d(TG3AG) quadruplexes plays an important role in the thermodynamic stabilization but a minor influence on the anti-HIV activity. Moreover, a detailed CD and DSC analyses indicate a monophasic behaviour for sequences I and V, while for ODNs (II–IV) clearly show that these quadruplex structures deviate from simple two-state melting, supporting the hypothesis that intermediate states along the dissociation pathway may exist
2014
Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG) Quadruplexes bearing hydrophobic tails at the 5'-end / Romanucci, Valeria; Milardi, D.; Campagna, T.; Gaglione, M.; Messere, Anna; D’Urso, A.; Crisafi, E.; La Rosa, C.; Zarrelli, Armando; Balzarini, J.; DI FABIO, Giovanni. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 22:3(2014), pp. 960-966. [10.1016/j.bmc.2013.12.051]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/572408
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