Self-assembling multicyclic peptides through metal binding

Constructing multicyclic peptides is challenging due to the large number of possible isomers that can form upon covalent bond formation. When these bonds are reversible, for example through metal coordination, the assembly process can become highly selective. We have already demonstrated this concept in complex systems such as epidermal growth factor (EGF), which, despite being theoretically capable of forming up to ten distinct derivatives upon incorporation of two bismuth atoms, selectively folds into its native structure. This project will investigate how multi-cysteine and selenocysteine-containing peptides and proteins interact with thiophilic metals such as bismuth, with the aim of understanding and exploiting self-assembly processes for the selective construction of multicyclic architectures.