Search

Your search keyword '"Brominated G-quadruplex"' showing total 2 results
Start Over Descriptor "Brominated G-quadruplex"
2 results on '"Brominated G-quadruplex"'

1. A more detailed picture of the interactions between virtual screening-derived hits and the DNA G-quadruplex: NMR, molecular modelling and ITC studies

Author

Trotta, Roberta, De Tito, Stefano, Lauri, Ilaria, La Pietra, Valeria, Marinelli, Luciana, Cosconati, Sandro, Martino, Luigi, Conte, Maria R., Mayol, Luciano, Novellino, Ettore, and Randazzo, Antonio

Subjects
*QUADRUPLEX nucleic acids, *DNA, *NUCLEAR magnetic resonance, *MOLECULAR models, *CALORIMETRY, *VOLUMETRIC analysis, *MOLECULAR structure, *CANCER treatment, *LIGANDS (Biochemistry)
Abstract

Abstract: The growing amount of literature about G-quadruplex DNA clearly demonstrates that such a structure is no longer viewed as just a biophysical strangeness but it is instead being considered as an important target for the treatment of various human disorders such as cancers or venous thrombosis. In this scenario, with the aim of finding brand new molecular scaffolds able to interact with the groove of the DNA quadruplex [d(TGGGGT)]4, we recently performed a successful structure-based virtual screening (VS) campaign. As a result, six molecules were found to be somehow groove binders. Herein, we report the results of novel NMR titration experiments of these VS-derived ligands with modified quadruplexes, namely [d(TGGBrGGT)]4 and [d(TGGGGBrT)]4. The novel NMR spectroscopy experiments combined with molecular modelling studies, allow for a more detailed picture of the interaction between each binder and the quadruplex DNA. Noteworthy, isothermal titration calorimetry (ITC) measurements on the above-mentioned compounds revealed that 2, 4, and 6 besides their relatively small dimensions bind the DNA quadruplex [d(TGGGGT)]4 with higher affinity than distamycin A, to the best of our knowledge, the most potent groove binder identified thus far. [Copyright &y& Elsevier]

Published
2011
Full Text
View/download PDF

2. A more detailed picture of the interactions between virtual screening-derived hits and the DNA G-quadruplex: NMR, molecular modelling and ITC studies

Author

Luigi Martino, Valeria La Pietra, Sandro Cosconati, Stefano De Tito, Maria R. Conte, Ilaria Lauri, Luciano Mayol, Roberta Trotta, Antonio Randazzo, Luciana Marinelli, Ettore Novellino, Trotta, R., De Tito, S., Lauri, Ilaria, LA PIETRA, Valeria, Marinelli, Luciana, Cosconati, S., Martino, L., Conte, M. R., Mayol, Luciano, Novellino, Ettore, Randazzo, Antonio, Trotta, R, De Tito, S, Lauri, I, La Pietra, V, Marinelli, L, Cosconati, Sandro, Martino, L, Conte, Mr, Mayol, L, Novellino, E, Randazzo, A., AAVV, Trotta, Roberta, DE TITO, Stefano, Martino, Luigi, and M. R., Conte

Subjects
Virtual screening, Models, Molecular, NMR titration, Magnetic Resonance Spectroscopy, Stereochemistry, Drug Evaluation, Preclinical, Calorimetry, G-quadruplex, Biochemistry, chemistry.chemical_compound, Nmr titration, Molecule, heterocyclic compounds, Binding site, Binding Sites, Chemistry, Distamycins, Isothermal titration calorimetry, General Medicine, Nuclear magnetic resonance spectroscopy, G-Quadruplexes, Crystallography, Brominated G-quadruplex, DNA
Abstract

The growing amount of literature about G-quadruplex DNA clearly demonstrates that such a structure is no longer viewed as just a biophysical strangeness but it is instead being considered as an important target for the treatment of various human disorders such as cancers or venous thrombosis. In this scenario, with the aim of finding brand new molecular scaffolds able to interact with the groove of the DNA quadruplex [d(TGGGGT)] 4, we recently performed a successful structure-based virtual screening (VS) campaign. As a result, six molecules were found to be somehow groove binders. Herein, we report the results of novel NMR titration experiments of these VS-derived ligands with modified quadruplexes, namely [d(TGG BrGGT)] 4 and [d(TGGGG BrT)] 4. The novel NMR spectroscopy experiments combined with molecular modelling studies, allow for a more detailed picture of the interaction between each binder and the quadruplex DNA. Noteworthy, isothermal titration calorimetry (ITC) measurements on the above-mentioned compounds revealed that 2, 4, and 6 besides their relatively small dimensions bind the DNA quadruplex [d(TGGGGT)] 4 with higher affinity than distamycin A, to the best of our knowledge, the most potent groove binder identified thus far. © 2011 Elsevier Masson SAS. All rights reserved.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results