Solution structure of a 2:1 complex of anticancer drug XR5944 with TFF1 estrogen response element: insights into DNA recognition by a bis-intercalator.

ABSTRACT: XR5944, a deoxyribonucleic acid (DNA) bis-intercalator with potent anticancer activity, can bind the estrogen response element (ERE) sequence to inhibit estrogen receptor-α activities. This novel mechanism of action may be useful for overcoming drug resistance to currently available antiestrogen treatments, all of which target the hormone-receptor complex. Here we report the nuclear magnetic resonance solution structure of the 2:1 complex of XR5944 with the naturally occurring TFF1-ERE, which exhibits important and unexpected features. In both drug-DNA complexes, XR5944 binds strongly at one intercalation site but weakly at the second site. The sites of intercalation within a native promoter sequence appear to be context and sequence dependent. The binding of one drug molecule influences t

SUBMITTER: Lin C 

PROVIDER: S-EPMC4027214 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature