Metal poisoning currently poses a significant challenge for medicinal chemistry. Although chelation therapy is the most efficient way to handle metal toxicity, the approved chelating agents still suffer from many drawbacks: The small molecule chelators do not distinguish between essential and toxic metal ions. As a result, most of these compounds are highly toxic, and many segments of the population are prohibited from treatment with them.

 

Peptides and short proteins serve as common scaffolds for metal detoxification in many organisms. As peptides are biocompatible, flexible, and contain a variety of potential functionalities, developing next-generation peptide-based chelating agents for this purpose may be highly advantageous. We aim to design non-toxic peptides for selective metal detoxification.

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We utilize various techniques and methods to achieve our goals, including bioinspired rational synthesis of novel unnatural amino acids and short peptides, survival-selection screening of large genetic peptide-encoding libraries, bioengineering, and natural product isolation.