Transition metal ions and metal–protein complexes

Transition metal ions, including iron, copper, zinc, and manganese, are vital micronutrients that serve as essential cofactors for approximately one-third of the human proteome (Maret, 2013). These ions are integrated into metal–protein complexes, or metalloproteins, where they facilitate critical biological processes such as oxygen transport, electron transfer, and enzymatic catalysis (Hoops et al., 2021). Dysregulation of metal ion homeostasis is linked to a range of pathologies, including neurodegenerative disorders like Alzheimer's disease, where metal-induced oxidative stress plays a role, and genetic conditions like Wilson's disease (Franz, 2013). In oncology, transition metals are targeted both through the use of chelators to deprive tumors of essential growth factors and via metal-based drugs like cisplatin that damage DNA (PubChem). Furthermore, many drugs function by inhibiting metalloenzymes, often by coordinating with the metal ion in the active site to prevent substrate binding (StatPearls, 2023). Consequently, these complexes represent a diverse and clinically significant class of therapeutic targets across multiple therapeutic areas.

Other names

MetalloproteinsMetal-binding proteinsBiometalsMetallocofactorsTrace metal ions

Drugs targeting these entities work through several mechanisms: chelation therapy involves ligands that bind and sequester free or loosely bound metal ions to facilitate their excretion; metalloenzyme inhibitors bind directly to the metal cofactor (e.g., zinc in ACE or carbonic anhydrase) to block catalytic activity; and metal-based chemotherapeutics (e.g., platinum compounds) form coordinate bonds with biological macromolecules like DNA to inhibit replication.