On the Biology of Werner's Complex

Angew Chem Int Ed Engl. 2021 Jul 26;60(31):17123-17130. doi: 10.1002/anie.202105019. Epub 2021 Jun 27.

Abstract

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.

Keywords: Antiviral efficacy; Biological Effects; DNA Binding and Condensation; Glycosaminoglycan interactions; Werner's Complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Cytomegalovirus / drug effects*
  • Fondaparinux / antagonists & inhibitors*
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / pharmacology*
  • Humans
  • Microbial Sensitivity Tests

Substances

  • Antiviral Agents
  • Coordination Complexes
  • Glycosaminoglycans
  • Fondaparinux