Non-Traditional Metallation of Metallothioneins with Xenobiotic Therapeutic Metals
Abstract
The rise of the Anthropocene has seen more global pollution than before in history. With the explosion of consumer electronics in the last half century, the rise of metal pollution from their extraction and disposal results in the unnatural introduction of heavy and rare metals into the ecosystem. Organisms have a metal defense protein, metallothionein, which has multiple roles in essential metal regulation and protection against minimal toxic metal exposure. However, these modern heavy metals prominent in electronics are not found biologically and their interactions in the body are generally unknown. Some of these metals are employed as therapeutic agents in the treatment of cancers, and as such this Thesis describes an investigation of therapeutic agents as models for heavy metal pollution to provide insight into the mechanisms of metal metabolism. Using electrospray ionization mass spectrometry and spectroscopic techniques, the binding of human metallothionein with the exotic metals platinum and rhodium is explored. Platinum and Rhodium bind readily to human metallothionein, raising concerns for toxicity.