Designed DNA probes from the neocarzinostatin family: Impact of glycosyl linkage stereochemistry on bulge base binding

The metabolite NCSi-gb of the natural product neocarzinostatin (NCS) shows strong binding affinity for two base bulges in DNA. Given the significance of DNA bulges in a variety of disease related processes, we undertook an examination of the structural requirements for bulge-drug binding. Using readily accessible mimics of NCSi-gb, we show that the stereochemistry of the aminolucosyl group plays a pivotal role, contributing to observed affinity and specificity of bulge binding.