Details

Autor(en) / Beteiligte

• Paiva, Raphael E. F.
• 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.

Titel

On the Biology of Werner's Complex

Ist Teil von

• Angewandte Chemie, 2021-07, Vol.133 (31), p.17260-17267

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• 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. Werner's Complex (WC) has hitherto unappreciated biological properties derived from its binding affinity to highly anionic biomolecules such as glycosaminoglycans (GAGs) and nucleic acids. In proof‐of‐principle it displays μm antiviral activity against human cytomegalovirus (HCMV) with promising selectivity. Exploitation of non‐covalent interactions has motivated the unprecedented discovery of the properties of this iconic compound.