On the Biology of Werner's Complex

Abstract

WernersC omplex, as ac ationic coordination complex (CCC), has hitherto unappreciated biological properties derived from its binding affinity to highly anionic biomolecules such as glycosaminoglycans (GAGs) and nucleic acids.C ompetitive 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. WernersC omplex is av ery efficient condensing agent for DNAa nd tRNA. In proof-of-principle for translational implications,i ti sd emonstrated to displaya ntiviral activity against human cytomegalovirus (HCMV) at micromolar concentrations with promising selectivity.E xploitation of non-covalent hydrogen-bonding and electrostatic interactions has motivated the unprecedented discovery of these properties, opening new avenues of researchf or this iconic compound.

Radiation induces ESCRT pathway dependent CD44v3+ extracellular vesicle production stimulating pro-tumor fibroblast activity in breast cancer

“…In addition, enzymatically treated IR-tEVs as well as IR-tEVs from Xylt1/2 KO failed to rescue ESCRT-dependent tEV deficient cells cocultured with fibroblasts ( Figure 6D ). The highly positively charged cobalt and platinum coordination compounds Werner’s Complex (WC) and Triplatin (TriPt) have been demonstrated to bind to HS, neutralizing its ability to interact with its molecular targets ( 28 , 49 ). Due to the dependence of IR-tEV activity on the HS side chains attached to CD44v3, we also examined whether these drugs might be able to mitigate their effects.…”

Cobalt(III)–Macrocyclic Scaffolds with Anti-Cancer Stem Cell Activity

“…Cobalt coordination complexes have been widely investigated for their biological activity over the last 50 years [ 2 , 3 , 4 ]. Doxovir (CTC-96) is a cobalt(III)–Schiff base complex that has recently passed phase II clinical trials for Herpes labialis (or herpes simplex virus 1) treatment [ 5 , 6 ]. It is the first cobalt-based compound to achieve this feat.…”