A novel assay to determine the sequence preference and affinity of DNA minor groove binding compounds.
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.
Thomas
Rita
R
Genelabs Technologies, Inc., Redwood City, CA 94063, USA.
Gonzalez
Carolyn
C
Roberts
Christopher
C
Botyanszki
Janos
J
Lou
Lillian
L
Michelotti
Emil F
EF
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018983:DNA Footprinting; D045647:DNA Glycosylases / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013379:Substrate Specificity; D051981:Uracil-DNA Glycosidase
D004214:Distamycins; D008024:Ligands; D009838:Oligodeoxyribonucleotides; C030000:stallimycin; D004247:DNA; D003850:Deoxyribonuclease I; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase