Cu(ii) binding to an antimicrobial shrimp peptide - a small step for structural chemistry, a big leap for medicinal applications.

PvHCt, a 23-amino acid long, histidine-rich peptide derived from shrimp, becomes strongly antimicrobial upon Cu(ii) ion binding. We describe Zn(ii) and Cu(ii) complexes of this peptide, aiming to understand how metal binding and structure correlates to biological activity. Using NMR, UV-vis, CD and FTIR spectroscopies, along with cyclic voltammetry, potentiometry, and DFT calculations, we demonstrate that Cu(ii) binds to the central and C-terminal regions of the peptide, inducing significant structural changes. These include a pronounced bend in the peptide backbone, increased α-helical content, and the production of reactive oxygen species, all of which contribute to the remarkable antimicrobial potency of PvHCt. In contrast, Zn(ii) binds to the C-terminal region with minimal impact on the peptide's overall structure, failing to enhance its antimicrobial activity.