Structural analysis of the binding modes of minor groove ligands comprised of disubstituted benzenes.
Two-dimensional homonuclear NMR was used to characterize synthetic DNA minor groove-binding ligands in complexes with oligonucleotides containing three different A-T binding sites. The three ligands studied have a C(2) axis of symmetry and have the same general structural motif of a central para-substituted benzene ring flanked by two meta-substituted rings, giving the molecules a crescent shape. As with other ligands of this shape, specificity seems to arise from a tight fit in the narrow minor groove of the preferred A-T-rich sequences. We found that these ligands slide between binding subsites, behavior attributed to the fact that all of the amide protons in the ligand backbone cannot hydrogen bond to the minor groove simultaneously.
Hawkins
C A
CA
Department of Chemistry and Graduate Group in Biophysics, University of California, Berkeley, CA 94720-1460, USA.
Watson
C
C
Yan
Y
Y
Gong
B
B
Wemmer
D E
DE
D020856:AT Rich Sequence / Q000235:genetics; D001483:Base Sequence; D001554:Benzene / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D009838:Oligodeoxyribonucleotides; D004247:DNA; D001554:Benzene