Comparison of the duplex-destabilizing effects of nucleobase-caged oligonucleotides

Nucleobase-caged oligonucleotide residues have photolabile “caging groups” that prevent the formation of Watson-Crick base pairs until the unmodified nucleobase is restored in a photolysis event. This principle can be used to put a growing variety of powerful nucleic acid-based applications under the precise spatiotemporal control using light as an addressing mechanism. Examples for applications include light control of transcription, RNAi, nucleic acid folding, primer extension, and restriction endonuclease as well as DNAzyme, aptamer, and antisense activity. However, a comparison of the duplex-destabilization properties of the various caged residues that have been used up to date and rules for achieving a maximal duplex destabilization with a minimum amount of modified residues are still missing. We present both a comparison of the duplex-destabilizing capabilities of various nucleobase-caged residues and address the question of influence on neighboring base pairs. [graphic removed]