A5002313358- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Click Chemistry and Applications
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Metal complexes synthesis and properties
- DNA Repair Mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- HIV/AIDS drug development and treatment
Dublin City University
2020-2025
Science Foundation Ireland
2023
Abstract Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition low micromolar cleavage activity. The BPL-C6 ligand was designed force two redox-active centres—central for enhancing AMN activity—to bind DNA, via...
Triplex-forming oligonucleotides (TFOs) are short, single-stranded oligomers that hybridise to a specific sequence of duplex DNA. TFOs can block transcription and thereby inhibit protein production, making them highly appealing in the field antigene therapeutics. In this work, primer extension protocol was developed enzymatically prepare chemical nuclease TFO hybrid constructs, with gene-silencing applications. Click chemistry employed generate novel artificial metallo-nuclease (AMN)-dNTPs,...
Limitations of clinical platinum(II) therapeutics include systemic toxicity and inherent resistance. Modern approaches, therefore, seek new ways to deliver active discrete nucleic acid targets. In the field antigene therapy, triplex-forming oligonucleotides (TFOs) have attracted interest for their ability specifically recognise extended duplex DNA Here, we report a click chemistry based approach that combines alkyne-modified TFOs with azide-bearing cis-platinum(II) complexes-based on...
The use of copper-based artificial nucleases as potential anticancer agents has been hampered by their poor selectivity in the oxidative DNA cleavage process. An alternative strategy to solve this problem is design systems capable selectively damaging noncanonical structures that play crucial roles cell cycle. We designed an oligocationic CuII peptide helicate binds and cleaves three-way junctions (3WJs) induces damage via a ROS-mediated pathway both vitro cellulo, specifically at...
In the field of nucleic acid therapy there is major interest in development libraries DNA-reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs CRISPR-Cas, but overcomes limitations imposed by delivery a large protein endonuclease required for DNA cleavage. Here, we introduce chemistry-based DNA-cleavage system comprising an artificial metallo-nuclease (AMN) oxidatively cuts DNA,...
The development of compounds that can selectively bind with non-canonical DNA structures has expanded in recent years. Junction DNA, including three-way junctions (3WJs) and four-way Holliday (HJs), offer an intriguing target for developmental therapeutics as both 3WJs HJs are involved replication repair processes. However, there a limited number assays available the analysis junction binding. Here, we describe design execution multiplex fluorescent polyacrylamide gel electrophoresis (PAGE)...
Abstract Limitations of clinical platinum(II) therapeutics include systemic toxicity and inherent resistance. Modern approaches, therefore, seek new ways to deliver active discrete nucleic acid targets. In the field antigene therapy, triplex‐forming oligonucleotides (TFOs) have attracted interest for their ability specifically recognise extended duplex DNA Here, we report a click chemistry based approach that combines alkyne‐modified TFOs with azide‐bearing cis ‐platinum(II) complexes—based...