On the Biology of Werner's Complex
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Peterson, Erica J
Malina, Jaroslav
Zoepfl, Mary
Hampton, J David
Johnson, Wyatt E
Graminha, Angelica
Ourahmane, Amine
McVoy, Michael A
Brabec, Viktor
Berners-Price, Susan J
Farrell, Nicholas P
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Abstract
Werner's Complex, as a cationic coordination complex (CCC), has hitherto unappreciated biological properties derived from its binding affinity to highly anionic biomolecules such as glycosaminoglycans (GAGs) and nucleic acids. Competitive inhibitor and spectroscopic assays confirm the high affinity to GAGs heparin, heparan sulfate (HS), and its pentasaccharide mimetic Fondaparinux (FPX). Functional consequences of this affinity include inhibition of FPX cleavage by bacterial heparinase and mammalian heparanase enzymes with inhibition of cellular invasion and migration. Werner's Complex is a very efficient condensing agent for DNA and tRNA. In proof-of-principle for translational implications, it is demonstrated to display antiviral activity against human cytomegalovirus (HCMV) at micromolar concentrations with promising selectivity. Exploitation of non-covalent hydrogen-bonding and electrostatic interactions has motivated the unprecedented discovery of these properties, opening new avenues of research for this iconic compound.
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Angewandte Chemie: International Edition
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This publication has been entered in Griffith Research Online as an advanced online version.
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Chemical sciences
Biological sciences
Antiviral efficacy
Biological Effects
DNA Binding and Condensation
Glycosaminoglycan interactions
Werner's Complex
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de Paiva, REF; Peterson, EJ; Malina, J; Zoepfl, M; Hampton, JD; Johnson, WE; Graminha, A; Ourahmane, A; McVoy, MA; Brabec, V; Berners-Price, SJ; Farrell, NP, On the Biology of Werner's Complex, Angewandte Chemie: International Edition, 2021