On the Biology of Werner's Complex

0555580 - BFÚ 2022 RIV DE eng J - Článek v odborném periodiku
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
Grant CEP: GA ČR(CZ) GC20-14082J
Institucionální podpora: RVO:68081707
Klíčová slova: heparan-sulfate * platinum complexes * cell-surface * dna-binding * entry * recognition * inhibition * chemistry
Obor OECD: Organic chemistry
Impakt faktor: 16.823, rok: 2021
Způsob publikování: Omezený přístup
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.
Trvalý link: http://hdl.handle.net/11104/0330042