A detailed understanding of the interactions between drugs and their targets is crucial to develop the best possible therapeutic agents. Structure-based drug design relies on the availability of high-resolution structures obtained primarily through X-ray crystallography. Collecting and analysing quickly a large quantity of structural data is crucial to accelerate drug discovery pipelines. Researchers from academia and industry can access the highly automated macromolecular crystallography (MX) beamlines of Diamond Light Source, the UK national synchrotron, to rapidly collect diffraction data from large numbers of crystals. With seven beamlines dedicated to MX, Diamond offers bespoke solutions for a wide variety of user requirements. Working in synergy with state-of-the-art laboratories and other life science instruments to provide an integrated offering, the MX beamlines provide innovative and multidisciplinary approaches to the determination of structures of new pharmacological targets as well as the efficient study of protein-ligand complexes.
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http://dx.doi.org/10.1016/j.ddtec.2020.10.003 | DOI Listing |
Acc Chem Res
January 2025
The Wolfson Catalysis Centre, Department of Chemistry, University of Oxford, Oxford OX1 3QR, U.K.
ConspectusThe discovery of reversible hydrogenation using metal-free phosphoborate species in 2006 marked the official advent of frustrated Lewis pair (FLP) chemistry. This breakthrough revolutionized homogeneous catalysis approaches and paved the way for innovative catalytic strategies. The unique reactivity of FLPs is attributed to the Lewis base (LB) and Lewis acid (LA) sites either in spatial separation or in equilibrium, which actively react with molecules.
View Article and Find Full Text PDFJ Virol
January 2025
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, Texas, USA.
Unlabelled: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein.
View Article and Find Full Text PDFOrg Lett
January 2025
Department of Catalysis and Fine Chemicals, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India.
We report the Pd-catalyzed and Ag-mediated temperature-dependent divergent synthesis of tetrahydropyrano[4,3-]pyran and hexahydrofuro[2,3-]pyran derivatives from a single substrate, alkynols. The reaction involves homocoupling of alkynols to form two C-O bonds and one C-C bond, resulting in tetrahydropyrano[4,3-]pyran cores at a high temperature (110 °C). Exposing tetrahydropyrano[4,3-]pyrans to a 200 W tungsten filament bulb yields tetrahydrofuro[2,3-]pyrans.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (M) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic M covalent inhibitors characterized by quinoline-based P moieties.
View Article and Find Full Text PDFProtein Sci
February 2025
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
We have recently demonstrated a novel anaerobic NADH-dependent haem breakdown reaction, which is carried out by a range of haemoproteins. The Yersinia enterocolitica protein, HemS, is the focus of further research presented in the current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into the mechanism of the novel breakdown process.
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