Synthesis, biophysical characterization and anti-HIV activity of d(TG(3)AG) Quadruplexes bearing hydrophobic tails at the 5 '-end
| Autor: | Armando Zarrelli, Giovanni Di Fabio, Jan Balzarini, Carmelo La Rosa, Emanuela Crisafi, Tiziana Campagna, Maria Gaglione, Alessandro D'Urso, Anna Messere, Danilo Milardi, Valeria Romanucci |
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| Přispěvatelé: | Romanucci, V, Milardi, D, Campagna, T, Gaglione, M, Messere, Anna, D’Urso, A, Crisafi, E, La Rosa, C, Zarrelli, A, Balzarini, J, Di Fabio, G., Romanucci, Valeria, Milardi, D., Campagna, T., Gaglione, M., D’Urso, A., Crisafi, E., La Rosa, C., Zarrelli, Armando, Balzarini, J., DI FABIO, Giovanni |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Anti-HIV activity
Aptamer Stereochemistry Anti-HIV Agents Clinical Biochemistry Drug Evaluation Preclinical Oligonucleotides Pharmaceutical Science Conjugated system Conjugated oligonucleotides HIV Envelope Protein gp120 G-quadruplex Biochemistry Aptamers Conjugated oligonucleotide Residue (chemistry) Structure-Activity Relationship Solid-phase synthesis Drug Discovery Humans heterocyclic compounds Molecular Biology Cells Cultured Serum Albumin Solid-Phase Synthesis Techniques Phosphoramidite Calorimetry Differential Scanning Dose-Response Relationship Drug Oligonucleotide Chemistry Circular Dichroism Organic Chemistry Aptamers Nucleotide Surface Plasmon Resonance Solid phase synthesis HIV Envelope Protein gp41 HIV Reverse Transcriptase Solid phase synthesi G-Quadruplexes Phosphodiester bond HIV-2 HIV-1 Molecular Medicine Thermodynamics Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Bioorganic & medicinal chemistry 22 (2014): 960–966. doi:10.1016/j.bmc.2013.12.051 info:cnr-pdr/source/autori:Romanucci, Valeria; Milardi, Danilo; Campagna, Tiziana; Gaglione, Maria; Messere, Anna; D'Urso, Alessandro; Crisafi, Emanuela; La Rosa, Carmelo; Zarrelli, Armando; Balzarini, Jan; Di Fabio, Giovanni/titolo:Synthesis, biophysical characterization and anti-HIV activity of d(TG(3)AG) Quadruplexes bearing hydrophobic tails at the 5 '-end/doi:10.1016%2Fj.bmc.2013.12.051/rivista:Bioorganic & medicinal chemistry (Print)/anno:2014/pagina_da:960/pagina_a:966/intervallo_pagine:960–966/volume:22 |
| DOI: | 10.1016/j.bmc.2013.12.051 |
| Popis: | Novel conjugated G-quadruplex-forming d(TG(3)AG) oligonucleotides, linked to hydrophobic groups through phosphodiester bonds at 5'-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 5'-end, conferring always improved stability to the quadruplex complex (20 < Delta Tm < 40 degrees 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(TG(3)AG) 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. (C) 2014 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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