Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0906532106 (2009)

A class of small molecules can distort the structure of DNA, disrupting its interaction with proteins that control gene expression.

Pyrrole–imidazole polyamides bind to the minor groove of the DNA double helix. David Chenoweth and Peter Dervan of the California Institute of Technology in Pasadena found that a cyclic polyamide binding in the minor groove compresses the major groove, which is where proteins called transcription factors bind DNA to regulate gene expression.

The polyamide also caused the helix to bend more than 18° towards the major groove, another distortion that could interfere with transcription-factor binding.