On the Biology of Werner's Complex

0555580 - BFÚ 2022 RIV DE eng J - Journal Article
de Paiva, R. E. F. - Peterson, E. J. - Malina, Jaroslav - Zoepfl, M. - Hampton, J. D. - Johnson, W. E. - Graminha, A. - Ourahmane, A. - McVoy, M. A. - Brabec, Viktor - Berners-Price, S.J. - Farrell, N.
On the Biology of Werner's Complex.
Angewandte Chemie - International Edition. Roč. 60, č. 31 (2021), s. 17123-17130. ISSN 1433-7851. E-ISSN 1521-3773
R&D Projects: GA ČR(CZ) GC20-14082J
Institutional support: RVO:68081707
Keywords : heparan-sulfate * platinum complexes * cell-surface * dna-binding * entry * recognition * inhibition * chemistry
OECD category: Organic chemistry
Impact factor: 16.823, year: 2021
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/anie.202105019

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.
Permanent Link: http://hdl.handle.net/11104/0330042