Probing the <i>hras</i>-1^Y i-motif with small molecules.

ABSTRACT: Non-B DNA structures represent intriguing and challenging targets for small molecules. For example, the promoter of the HRAS oncogene contains multiple G-quadruplex and i-motif structures, atypical globular folds that serve as molecular switches for gene expression. Of the two, i-motif structures are far less studied. Here, we report the first example of small organic compounds that directly interact with the hras-1^Y i-motif. We use a small molecule microarray screen to identify drug-like small molecules that bind to the hras-1^Y i-motif but not to several other DNA or RNA secondary structures. Two different lead compounds, 1 and 2, were discovered to have 7.4 ± 5.3 μM and 5.9 ± 3.7 μM binding affinity by surface plasmon resonance and

SUBMITTER: Journey SN 

PROVIDER: S-EPMC6301200 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature