DNA is often referred to as the molecule of life, since it contains the instructions for making the required proteins. However, it is not simply a (genetic) code to be read; its structure has an important role in determining when and how much of a particular 5 protein is made at any point in time. Furthermore, there are a range of special DNA structures, e.g. Holliday junctions, which play essential roles for the existence of life as we know it or as it will become. In this tutorial review the normal B-DNA structure is summarised and metallomolecule binding modes discussed then used as a basis for examining DNA structures which can be induced by molecules containing metallic cations. The effects of aquated metal ions, cobalt ammine and ruthenium octahedral metal complexes, metallo helicates and platinum complexes such as cis-platin are discussed alongside techniques such as NMR, 10 X-ray crystallography, gel electrophoresis, circular dichroism, linear dichroism and molecular dynamics.

Multidrug resistance of bacterial pathogens is a major problem and there is a clear need for the development of new types of antibiotics. Here we investigated the antimicrobial activity of ruthenium(II) based DNA-intercalating complexes. These complexes were found to have no activity in vitro against the Gram-negative bacterium Escherichia coli, but the complexes were clearly active against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. In vivo activity has also been demonstrated for one of the compounds using a simple infection model, the nematode Caenorhabditis elegans. Importantly, this also showed that the compound tested was not toxic to the nematodes.

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Persistence length is the foremost measure of DNA flexibility. Its origins lie in polymer theory which was adapted for DNA following the determination of B-DNA structure in 1953. There is no single definition of persistence length used, and the links between published definitions are based on assumptions which may, or may not be, clearly stated. DNA flexibility is affected by local ionic strength, solvent environment, bound ligands and intrinsic sequence-dependent flexibility. This article is a review of persistence length providing a mathematical treatment of the relationships between four definitions of persistence length, including: correlation, Kuhn length, bending, and curvature. Persistence length has been measured using various microscopy, force extension and solution methods such as linear dichroism and transient electric birefringence. For each experimental method a model of DNA is required to interpret the data. The importance of understanding the underlying models, along with the assumptions required by each definition to determine a value of persistence length, is highlighted for linear dichroism data, where it transpires that no model is currently available for long DNA or medium to high shear rate experiments.

Global fatalities related to COVID-19 are expected to be high in 2020–2021. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase II and phase III trials could take less long to conduct if they used human challenge methods—that is, deliberately infecting participants with COVID-19 following inoculation. This article analyses arguments for and against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approval processes so that they are in place when applications for trials are made.

Global fatalities related to COVID-19 are expected to be high in 2020-21. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase 2 and Phase 3 trials could take less long to conduct if they used human challenge methods – that is, deliberately infecting participants with COVID-19 following inoculation.This article analyses arguments for and against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approvals processes so that they are in place when applications for trials are made.

DNA is often referred to as the molecule of life, since it contains the instructions for making the required proteins. However, it is not simply a (genetic) code to be read; its structure has an important role in determining when and how much of a particular 5 protein is made at any point in time. Furthermore, there are a range of special DNA structures, e.g. Holliday junctions, which play essential roles for the existence of life as we know it or as it will become. In this tutorial review the normal B-DNA structure is summarised and metallomolecule binding modes discussed then used as a basis for examining DNA structures which can be induced by molecules containing metallic cations. The effects of aquated metal ions, cobalt ammine and ruthenium octahedral metal complexes, metallo helicates and platinum complexes such as cis-platin are discussed alongside techniques such as NMR, 10 X-ray crystallography, gel electrophoresis, circular dichroism, linear dichroism and molecular dynamics.

No abstract