In this research project, the chemical diversity of catalytic short DNA molecules (DNAzymes) will be expanded through a reversible and pH-controlled reaction with aldehydes. This dynamic derivatization step can be carried out on previously reported DNAzymes or included as part of the directed evolution cycle to find new ones. The aldehydes can bear virtually any functional groups, organometallic ones being particularly interesting owing to their potential of replacing metal ion cofactors and their elusiveness to the state-of-the-art methods of DNAzyme synthesis. During the project, RNA and DNA ligation and site-specific RNA deamination will serve as testbed reactions, but in the future the proposed method could be used to develop DNAzymes with improved activity for any reaction.

2026

2030