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On the Biology of Werner's Complex
Author(s) -
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,
BernersPrice Susan J.,
Farrell Nicholas P.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202105019
Subject(s) - heparan sulfate , chemistry , nucleic acid , biomolecule , cationic polymerization , dna , biochemistry , covalent bond , glycosaminoglycan , organic chemistry
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.