Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers.
Int J Mol Sci
; 22(12)2021 Jun 17.
Article
in En
| MEDLINE
| ID: mdl-34204214
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 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 c-myc 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Carbazoles
/
Macromolecular Substances
/
G-Quadruplexes
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Document type:
Article
Affiliation country:
Italia