Design of an oligosaccharide scaffold that binds in the minor groove of DNA

Many biological recognition events involve extensive interactions between m acromolecules. Strategies to design compounds that mimic large peptides or other elements of secondary structure could be useful for blocking interact ions between large surfaces. In this paper, the use of oligosaccharides as scaffolds for the design of peptidomimetics is addressed. A functionalized oligosaccharide modeled after a basic region peptide helix has been designe d and synthesized. This oligosaccharide binds to duplex DNA with micromolar affinity. The mode of binding has been established by 2D NMR, and shows th at the oligosaccharide binds DNA in the minor groove with one surface of th e oligosaccharide contacting the floor of the DNA.