Targeting RNA with Conformationally Restricted Oligonucleotides

A configurational and conformational complementarity between targeted ssRNA and the antisense oligonucleotide is a prerequisite for efficient hybridization. In the design of oligonucleotides that may hybridize strongly with natural RNA, one may select molecules with a preorganized structure. The hybridization process should then benefit from less negative entropy changes during duplex formation. Although, it is by now not completely clear which conformational restricted motif is best suited for this purpose, the N3′–P5′ phosphoramidate linkage and the hexitol nucleic acids seems to gain the objective.