Replacement of the cleavable phosphodiester bond of a hammerhead ribozyme substrate by an amide linkage

A nucleoside dimer in which the natural phosphodiester bond is replaced by an isosteric amide linkage has been prepared. This dimer analogue was subse quently incorporated chemically at the cleavage position of a hammerhead ri bozyme substrate. Although the resulting substrate analogue exhibited a hig h affinity for the ribozyme as shown by gel retardation assays, the amide b ond proved to be fully resistant to cleavage under standard conditions of r ibozyme cleavage activity.