A1 Refereed original research article in a scientific journal
Influence of conjugation and other structural changes on the activity of Cu2+ based PNAzymes
Authors: Ghidini A, Murtola M, Stromberg R
Publisher: ROYAL SOC CHEMISTRY
Publication year: 2016
Journal: Organic and Biomolecular Chemistry
Journal name in source: ORGANIC & BIOMOLECULAR CHEMISTRY
Journal acronym: ORG BIOMOL CHEM
Volume: 14
Issue: 9
First page : 2768
Last page: 2773
Number of pages: 6
ISSN: 1477-0520
DOI: https://doi.org/10.1039/c5ob02394g
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.