Molecular methods for assessment of non-covalent metallodrug-DNA interactions
| Autor: | Creina Slator, Vickie McKee, Zara Molphy, Nicholas Farrell, Andrew Kellett |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Circular dichroism 02 engineering and technology Computational biology 010402 general chemistry 01 natural sciences Phosphates chemistry.chemical_compound Coordination Complexes Phosphates/chemistry Molecule Humans DNA/chemistry Platinum Molecular Structure Drug discovery Chemistry General Chemistry Nuclear magnetic resonance spectroscopy DNA Platinum/chemistry 021001 nanoscience & nanotechnology Coordination Complexes/chemistry Small molecule Intercalating Agents 3. Good health 0104 chemical sciences Direct methods Drug Design Nucleic acid Intercalating Agents/chemistry Copper/chemistry 0210 nano-technology Copper |
| Zdroj: | Kellett, A, Molphy, Z, Slator, C, McKee, V & Farrell, N P 2019, ' Molecular methods for assessment of non-covalent metallodrug-DNA interactions ', Chemical Society Reviews, vol. 48, no. 4, pp. 971-988 . https://doi.org/10.1039/c8cs00157j Chemical Society Reviews |
| DOI: | 10.1039/c8cs00157j |
| Popis: | Herein we provide an accessible account of molecular methods to probe inorganic–nucleic acid interactions. Techniques are described using copper(ii) and platinum(ii) complexes prepared in our laboratories. The binding of small molecule metallodrugs to discrete regions of nucleic acids is an important branch of medicinal chemistry and the nature of these interactions, allied with sequence selectivity, forms part of the backbone of modern medicinal inorganic chemistry research. In this tutorial review we describe a range of molecular methods currently employed within our laboratories to explore novel metallodrug–DNA interactions. At the outset, an introduction to DNA from a structural perspective is provided along with descriptions of non-covalent DNA recognition focusing on intercalation, insertion, and phosphate binding. Molecular methods, described from a non-expert perspective, to identify non-covalent and pre-associative nucleic acid recognition are then demonstrated using a variety of techniques including direct (non-optical) and indirect (optical) methods. Direct methods include: X-ray crystallography; NMR spectroscopy; mass spectrometry; and viscosity while indirect approaches detail: competitive inhibition experiments; fluorescence and absorbance spectroscopy; circular dichroism; and electrophoresis-based techniques. For each method described we provide an overview of the technique, a detailed examination of results obtained and relevant follow-on of advanced biophysical/analytical techniques. To achieve this, a selection of relevant copper(ii) and platinum(ii) complexes developed within our laboratories are discussed and are compared, where possible, to classical DNA binding agents. Applying these molecular methods enables us to determine structure–activity factors important to rational metallodrug design. In many cases, combinations of molecular methods are required to comprehensively elucidate new metallodrug–DNA interactions and, from a drug discovery perspective, coupling this data with cellular responses helps to inform understanding of how metallodrug–DNA binding interactions manifest cytotoxic action. |
| Databáze: | OpenAIRE |
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