Groove Binding

The DNA helix has two grooves of different size, the minor and the major grooves, which may serve as binding sites for guest molecules. Whereas relatively large molecules such as proteins bind preferentially to the major groove of DNA [4], the minor groove is the preferred binding site for small ligands [1c, 3]. The binding pocket of a DNA groove is defined by two different regions, the ''bottom'', formed by the edges of the nucleic bases that face into the groove, and the ''walls'', which are formed from the deoxyribose-phosphate backbone of the DNA. Groove binders usually consist of at least two aromatic or heteroaromatic rings whose connection allows conformational flexibility such that a crescent-shaped conformation may be achieved and the molecule fits perfect into the groove. In addition, functional groups are required to form hydrogen bonds with the nucleic bases at the bottom of the groove. Typical minor-groove binders are Hoechst 33258 (6) [18] and netrop-sin 7 [19].

Most groove binders have binding selectivity toward AT-rich areas, because grooves, which consist of GC base pairs, are sterically hindered by the guanine amino functionality at C-2 and its hydrogen bond with the C-2 carbonyl functionality of

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