Glycosaminoglycan-directed cobalt complexes.

The biological activity of the 6+ Co containing Werner's Complex has been described and mechanistic considerations suggest that the highly anionic glycosaminoglycans (heparan sulfate, HS, GAGs) are implicated in this activity [Paiva et al. 2021]. To examine in detail the molecular basis of Werner's Complex biological properties we have examined a selection of simple mononuclear Co compounds for their interactions with HS and Fondaparinux (FPX).

Metalloglycomics of tris(2,2'-bipyridyl) cobalt and ruthenium compounds.

Metal complexes studied to date under the framework of metalloglycomics belong to the M-NH general motif (polynuclear platinum compounds; Werner's complex), acting mainly as cationic hydrogen bonding species toward glycosaminoglycans (GAGs), an interaction termed metalloshielding. In this paper, we expand our studies to substitution-inert octahedral cobalt(III) and ruthenium(II) complexes bearing the non‑hydrogen-donor ligand 2,2'-bipyridine (bpy). We identified by NMR spectroscopy that [Co(bpy)] binds to the highly sulfated synthetic pentasaccharide, Fondaparinux (FPX), while no major perturbations are found in the presence of [Ru(bpy)].

On the Biology of Werner's Complex.

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.

Metal ions and the extracellular matrix in tumor migration.

In this review, we explore the roles of divalent metal ions in structure and function within the extracellular matrix (ECM), specifically, their interaction with glycosaminoglycans (GAGs) during tumor progression. Metals and GAGs have been individually associated with physiological and pathological processes, however, their combined activities in regulating cell behavior and ECM remodeling have not been fully explored to date. During tumor progression, divalent metals and GAGs participate in central processes, such as cell migration and angiogenesis, either by modulating cell surface molecules, as well as soluble signaling factors.

Substitution-Inert Polynuclear Platinum Complexes as Metalloshielding Agents for Heparan Sulfate.

Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase modulates tumour-related events including angiogenesis, cell invasion, and metastasis. Metalloshielding of heparan sulfate (HS) by positively charged polynuclear platinum complexes (PPCs) effectively inhibits physiologically critical HS functions. Studies using bacterial P.

Comparison of Metal-Ammine Compounds Binding to DNA and Heparin. Glycans as Ligands in Bioinorganic Chemistry.

We present spectroscopic and biophysical approaches to examine the affinity of metal-ammine coordination complexes for heparin as a model for heparan sulfate (HS). Similar to nucleic acids, the highly anionic nature of heparin means it is associated in vivo with physiologically relevant cations, and this work extends their bioinorganic chemistry to substitution-inert metal-ammine compounds (M). Both indirect and direct assays were developed.