SUBTLE ATOMIC GROUP DISCRIMINATION IN THE RNA MINOR-GROOVE

As a problem in molecular recognition and for drug discovery, great in terest has developed around the possibility that RNA structures could be discriminated by peptides and other small molecules. Although small peptides have been shown to have the capacity to discriminate specifi c bulges and loops in RNA molecules, discrimination of double helical regions by a peptide binder has not been reported. Indeed, the most ac cessible part of an RNA helix is the minor groove, and fundamental ste reochemical considerations have suggested that discrimination of at le ast some base pairs would be difficult in the minor groove. Here we re port the design and isolation of a peptide binder that manifests the m ost subtle kind of discrimination of base pair differences in the RNA minor groove. Functional discrimination of a single atomic group is de monstrated as well as the difference between two different angular ori entations of the same group, This report of RNA helix discrimination b y a peptide binder suggests a richer potential for RNA minor groove re cognition than previously thought.