Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed1H and31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.

Exploring the interaction of curaxin cbl0137 with g-quadruplex dna oligomers / S. Dallavalle, L.M. Mattio, R. Artali, L. Musso, A. Avino, C. Fabrega, R. Eritja, R. Gargallo, S. Mazzini. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:12(2021 Jun 17), pp. 6476.1-6476.15. [10.3390/ijms22126476]

Exploring the interaction of curaxin cbl0137 with g-quadruplex dna oligomers

Dallavalle S.;Mattio L. M.;Artali R.;Musso L.;Mazzini S.
2021-06-17

Abstract

Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed1H and31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.
C-myc; Circular dichroism; Curaxin; DNA interactions; G-quadruplex; Molecular modeling; NMR spectroscopy
Settore CHIM/06 - Chimica Organica
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/854268
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