RESUMEN
We have previously shown that PNA-neocuproine conjugates can act as artificial RNA restriction enzymes. In the present study we have additionally conjugated the PNA with different entities, such as oligoethers, peptides etc. and also constructed systems where the PNA is designed to clamp the target RNA forming a triplex. Some conjugations are detrimental for the activity while most are silent which means that conjugation can be done to alter physical properties without losing activity. Conjugation with a single oligoether close to the neocuproine does enhance the rate almost twofold compared to the system without the oligoether. The systems designed to clamp the RNA target by forming a triplex retain the activity if the added oligoT sequence is 5 PNA units or shorter and extends the arsenal of artificial RNA restriction enzymes. Changing the direction of a closing base pair, where the target RNA forms a bulge, from a GC to a CG pair enhances the rate of cleavage somewhat without compromising the selectivity, leading to the so far most efficient artificial nuclease reported.
Asunto(s)
Cobre/metabolismo , Compuestos Organometálicos/metabolismo , Ácidos Nucleicos de Péptidos/metabolismo , Ribonucleasas/química , Ribonucleasas/metabolismo , Cobre/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Ácidos Nucleicos de Péptidos/química , ARN/química , ARN/metabolismo , Ribonucleasas/síntesis químicaRESUMEN
Presented is our most recent work on synthesis and properties of oligonucleotide analogues and conjugates These include 2'-carbamoylmethyl derivatives, peptideoligonucleotide conjugates and conjugates made to combine Watson-Crick and non-Watson-Crick interactions as well as conjugates with RNA-cleaving groups. Recent results on cleavage of RNA by artificial nucleases, is also presented.