The molecular basis for pyrimidine-selective DNA binding: Analysis of calicheamicin oligosaccharide derivatives by capillary electrophoresis

Synthetic derivatives of the calicheamicin oligosaccharide were designed to probe the molecular basis for pyrimidine recognition. Binding affinities of the oligosaccharide derivatives for a range of DNA sequences were determined using capillary electrophoresis. The results show that having an iodo-substituted C-ring is neither necessary nor sufficient for pyrimidine-selective binding. Pyrimidine-selective binding depends on maintaining the overall shape and rigidity of the calicheamicin oligosaccharide. These experiments support the proposal that the novel pyrimidine selectivity of calicheamicin is the result of a shape-dependent induced-fit interaction with DNA sequences.