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 a nd the head-to-head dimer of this oligosaccharide are known to bind to the minor groove of DNA in a sequence-selective manner preferring dis tinct target sequences, We tested these carbohydrates for their abilit y to interfere with transcription factor function. The oligosaccharide s inhibit binding of transcription factors to DNA in a sequence-select ive manner, probably by inducing a conformational change in DNA struct ure. They also interfere with transcription by polymerase II in vitro. The effective concentrations of the oligosaccharides for inhibition o f transcription factor binding and for transcriptional inhibition are in the micromolar range. The dimer is a significantly more active inhi bitor than is the monomer.