Cationic polynuclear platinum complexes (PPCs) have high affinity for the highly anionic glycosaminoglycans (GAGs) such as heparan sulfate (HS) and chondroitin sulfates (CS) on the cell surface. The high expression of GAGs in many tumors can be exploited for selective tumor uptake of PPCs compared to the neutral clinically approved drugs cisplatin and carboplatin in ovaraian and triple-negative breast cancer. This feature allows an approach to overcome cisplatin/carboplatin resistance in a clinical setting. Further, metalloshielding of heparan sulfate may enhance antiviral activities of PPCs, for  many viruses including human cytomegalovirus and SARS Cov2 where HS is implicated as receptor for viral attachment and entry, suggesting potential as a new class of broad-spectrum antivirals. These features are properties of charged coordination complexes (CCCs) in general, which has led to description of the unique biological properties of the iconic  6+ Werner’s Complex (hexol). This presentation summarises our work and that of our collaborators in this area including fundamental studies on metal ion-GAG interactions, an overlooked area compared to that of nucleic acids and proteins.

Exploiting the glycosaminoglycan interactome for precision medicine for anticancer platinums and inorganic chemistry

ACS Spring 2022

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