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dissemination

New publication on Angew. Chem from Reading-Dublin collaboration

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Tayler David Prieto (ESR2, University of Reading) published, together with colleagues from the Cardin group in Reading and the Kellett group at DCU, a paper on Angewandte Chemie (International Edition) titled “Probing a major DNA weakness: resolving the groove and sequence selectivity of the diimine complex [Λ-Ru(phen)2phi]2+”. This work notably benefitted from the use of the infrastructure at Diamond Light Source Ltd.

The paper demonstrates, for the first time, a crystal structure showing groove selectivity by an intercalating ruthenium complex.

It is available in Open Access on the publisher’s website.

Work from Paris-Reading collaboration published in Inorganic Chemistry

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Our ESRs Maria Dalla Pozza (PSL University), Tayler David Prieto and Ahmad Abdullrahman (University of Reading) published together with their supervisors and co-authors from the Hollenstein lab at Institut Pasteur, a new article in the Inorganic Chemistry journal.

The article is about Ru(II) complexes with phototoxicity in the nM concentration range.

Jamie and colleagues at Origins of Life Donostia Meeting 2023

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Our ESR Chun Yin (Jamie) Chan from the Carell group at LMU Munich, together with colleagues presented their work at the Origins of Life Donostia Meeting in Donostia-San Sebastian, Basque Country (Spain).

He presented his work on “RNA modifications as molecular fossils of an early protocell world”, co-authored with Johannes Singer and Thomas Carell.

New publication on super cytotoxic Re(I) complexes

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Collaborative work between researchers from the University of the Free World in South Africa and the Gasser group at PSL University has just been published in Inorganic Chemistry. This work notably includes a contribution from our ESR Maria Dalla Pozza.

This paper presents Re(I) carbonyl complexes with exceptionally low nanomolar cytotoxic activity toward prostate cancer cells, demonstrating further the future viability of utilising rhenium in the fight against cancer.

It is available Open Access here.

DCU and LMU publish review on Third Generation Sequencing of Epigenetic DNA

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The Kellett (DCU) and Carell (LMU) groups recently published a collaborative review titled ‘Third Generation Sequencing of Epigenetic DNA’ in Angewandte Chemie. The review is open access and covers the latest developments in sequencing techniques adapted and developed for ‘third generation’ sequencing platforms, which promise to provide the fastest and most convenient means of DNA sequencing to date.

Cytosine modifications have been shown to influence gene regulation, in turn effecting disease and development, thus facile methods for sequencing these base modifications by exploiting the chemistries of these new devices is an active area of research. Despite extensive reviews covering sequencing technologies and base modifications independently, to our knowledge, this is the first publication to highlight the emerging potential of third generation sequencing technologies to expedite epigenetic research.

During the first in-person NATURE-ETN training week organised in the Institute for Chemical Epigenetic – Munich (ICE-M), Dr Markus Müller and Dr. Pascal Giehr delivered seminars focused on epigenome sequencing which provided valuable background in techniques developed to facilitate the decoding of this secondary information layer in DNA. Work Package 3 in NATURE-ETN aims to generate new techniques for sequencing and imaging epigenetic bases. DCU and LMU have access to third generation sequencing devices, so this review will provide a helpful reference point for researchers in the network.  

New publication examines the multi-modal activity of copper(II) and silver (I)-phendione complexes on DNA scission within P. aeruginosa

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Recent collaborative work from NATURE-ETN has been published in the Journal of Biological Inorganic Chemistry by researchers in the Kellett lab at DCU. Co-authors include NATURE-ETN coordinator Dr. Andrew Kellett, co-supervisor Dr. Georgia Menounou, and ESR Conor Bain. The paper investigated the multi-modal activity of copper(II) and silver(I) complexes with the N,N-coordinating ligand, 1,10-phenanthroline-5,6-dione, with particular focus on DNA damage within Pseudomonas aeruginosa.

The emergence of microbial drug-resistance in recent decades has given rise to the need for novel antimicrobial therapeutics. The metal-based complexes [Ag(1,10-phenanthroline-5,6- dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione) have previously demonstrated efficient antimicrobial action against multidrug-resistant species. The focus of the study was to understand the binding potential of these complexes with double-stranded DNA using a combination of in silico and in vitro approaches. Promising results arising from this work revealed a potentially new class of antimicrobial drug candidate with a distinct therapeutic mechanism against the multidrug-resistant pathogen P. aeruginosa.

Molecular docking studies showed both complexes elicit a multi-mechanistic approach to DNA-binding via hydrogen bonding, hydrophobic and electrostatic interactions, with both complexes favouring minor groove binding. Of the two complexes, Cu-phendione achieved the highest binding affinity for both major and minor grooves with nearly 10x greater affinity to DNA than Ag-phendione and nearly 20x greater affinity than the phendione ligand alone. Cu-phendione achieved DNA scission through free radical oxidative damage, as well as DNA-nicking and relaxation of supercoiled plasmid DNA. It was concluded that both complexes elicit a dose-dependent effect, with successful DNA fragmentation within multi-drug resistant pathogen P. aeruginosa when treated with a single dose of Cu-phendione. This work proposes a novel dose-regulated class of metal-based antimicrobial therapeutics.

Reference:

Galdino, A.C.M., Viganor, L., Pereira, M.M., Devereux, M., McCann, M., Branquinha, M.H., Molphy, Z., O’Carroll, S., Bain, C., Menounou, G., Kellett, A., Dos Santos, A.L.S. Copper(II) and silver(I)-1,10-phenanthroline-5,6-dione complexes interact with double-stranded DNA: further evidence of their apparent multi-modal activity towards Pseudomonas aeruginosa. J Biol Inorg Chem (2022). https://doi.org/10.1007/s00775-021-01922-3