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.

Department of Biochemistry and Molecular Biology Virginia Commonwealth University Richmond Virginia 23298 0033 USA

Department of Chemistry Virginia Commonwealth University Richmond VA 23284 2006 USA

Department of Pediatrics Virginia Commonwealth University Richmond VA 23298 0163 USA

Institute for Glycomics Griffith University Gold Coast Campus Southport Qld 4222 Australia

Institute of Biophysics Czech Academy of Sciences Kralovopolska 135 61265 Brno Czech Republic

Massey Cancer Center Virginia Commonwealth University Richmond VA 23298 0037 USA

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