Improving the structure of organomercury oligonucleotide conjugates for ribonuclease activity

Abstract

Artificial ribonucleases are a class of artificial RNA molecules capable of catalysing the cleavage of specific RNA phosphodiester bonds. The discovery and study of artificial ribonuclease have had a major impact on the fields of biology and medicine. Similar to natural nucleases, artificial ribonucleases recognise and bind target RNA molecules and catalyse chemical reactions at specific sites. However, artificial ribonucleases offer greater design and modification flexibility than natural ribonucleases. Unlike state-of-the-art artificial ribonucleases modified with copper and zinc metal ions, organomercury residue was chosen as the catalytic group in this project. This project aimed to optimise the structure of organomercury-conjugated artificial ribonucleases to enhance the cleavage activity towards target oligonucleotides. The organomercury catalytic groups were conjugated between the oligonucleotide chains rather than at the chain termini. Four artificial ribonucleases with different sequences, each conjugated with organomercury complex in the middle were synthesised and their catalytic activity in the cleavage of target oligonucleotides is still in the process of evaluation.