Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function.
The synthetic oligosaccharide moiety of the antibiotic calicheamicin and the head-to-head dimer of this oligosaccharide are known to bind to the minor groove of DNA in a sequence-selective manner preferring distinct target sequences. We tested these carbohydrates for their ability to interfere with transcription factor function. The oligosaccharides inhibit binding of transcription factors to DNA in a sequence-selective manner, probably by inducing a conformational change in DNA structure. They also interfere with transcription by polymerase II in vitro. The effective concentrations of the oligosaccharides for inhibition of transcription factor binding and for transcriptional inhibition are in the micromolar range. The dimer is a significantly more active inhibitor than is the monomer.
Liu
C
C
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Smith
B M
BM
Ajito
K
K
Komatsu
H
H
Gomez-Paloma
L
L
Li
T
T
Theodorakis
E A
EA
Nicolaou
K C
KC
Vogt
P K
PK
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D004247:DNA / Q000378:metabolism*; D004257:DNA Polymerase II / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D053281:Enediynes; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D053281:Enediynes; D009838:Oligodeoxyribonucleotides; D009844:Oligosaccharides; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; C055955:calicheamicin gamma(1)I; D004247:DNA; D004257:DNA Polymerase II