Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers

• Main Authors: Sabrina Dallavalle, Luce M. Mattio, Roberto Artali, Loana Musso, Anna Aviñó, Carme Fàbrega, Ramon Eritja, Raimundo Gargallo, Stefania Mazzini
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: curaxin; NMR spectroscopy; circular dichroism; G-quadruplex; molecular modeling; DNA interactions
• Online Access: https://www.mdpi.com/1422-0067/22/12/6476

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 by ¹H 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 <i>c</i>-<i>myc</i> promoter Pu22 sequence. We also performed ¹H and ³¹P 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.