Identifying and characterizing the biological targets of metallotherapeutics: Two approaches using Au(I)-protein
1University of Southern California, Los Angeles, CA 90089, USA.
Abstract:
A significant challenge in the field of medicinal inorganic chemistry is the identification of biological targets of metal-based drugs and the characterization of the metal-biomolecule adducts. A classic example is Au(I), which has long been used to treat rheumatoid arthritis despite a poor understanding of its biological targets due to the lability, reactivity, and "spectroscopic silence" that are characteristic of Au(I). Here, we report two qualitative methods for characterizing Au(I)-protein adducts: a thiol-reactive probe that facilitates the identification of biological cysteine-Au(I) adducts and a photoreactive Au(I) complex that produces a covalent bond between the Au(I) complex and the biomolecule.
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