Published online 12 January 2004
Nucleic Acids Research, 2004, Vol. 32, No. 1 e8
© 2004 Oxford University Press
A novel assay to determine the sequence preference and affinity of DNA minor groove binding compounds
Genelabs Technologies, Inc., Redwood City, CA 94063, USA
*To whom correspondence should be addressed. Tel: +1 650 562 1401; Fax: +1 650 562 1531; Email: emilm{at}genelabs.com
Sequence-specific binding in the minor groove of DNA by small molecules is a growing area of research with possible therapeutic relevance. By selectively binding to DNA sequences required by critical transcription factors, these small molecules could potentially modulate the expression levels of disease-causing genes. Precise targeting of a critical transcription factor of a selected gene requires an understanding of the preferred sequence of the DNA binding compound. As new compounds are being synthesized, there is a need to evaluate their DNA recognition profile. We sought to establish a procedure to determine sequence preference of compounds with previously unknown binding properties. A novel procedure for determining the optimal DNA binding sequence of minor groove binding compounds is described here. The assay also allows for determination of the binding affinity to a particular sequence.