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On the Biology of Werner's Complex

REF. de Paiva, EJ. Peterson, J. Malina, M. Zoepfl, JD. Hampton, WE. Johnson, A. Graminha, A. Ourahmane, MA. McVoy, V. Brabec, SJ. Berners-Price, NP. Farrell

. 2021 ; 60 (31) : 17123-17130. [pub] 20210627

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22004059

Grantová podpora
P30 CA016059 NCI NIH HHS - United States
P30 CA016059 NIH HHS - United States

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.

Citace poskytuje Crossref.org

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