Insight into the role of metal coordination in the bioactivity of calcitermin derivatives

Antibiotics are undoubtedly one of the most important weapons to fight infectious diseases. However, the phenomenon of antimicrobial resistance has forced to reevaluate their clinical use. Antimicrobial peptides are promising alternatives to classical antibiotics. Their microbicidal activity can arise from different mechanisms, one of which is known as nutritional immunity and has metal micronutrients and metal-binding biomolecules as its main players. The human antimicrobial peptide calcitermin (VAIALKAAHYHTHKE) has been previously studied by our research group to evaluate its metal chelating ability and bioactivity against various pathogenic microorganisms [1]. Afterwards, a systematic study was undertaken on calcitermin derivatives. Modifications in the amino acid sequence of the native peptide have been introduced with the aim of verifying the impact of Cu(II) and Zn(II) ions on the stability, coordination and antimicrobial activity of the formed complexes [2,3]. After peptide synthesis and purification, a deep investigation of complex formation equilibria and coordination chemistry of the formed species has been obtained by means of potentiometric titrations, mass spectrometry, UV-Vis, circular dichroism and electronic paramagnetic resonance. Antimicrobial assays provided information on the bioactivity of the compounds against a wide panel of microorganisms. Our results highlight the crucial role of metal ions in enhancing the antimicrobial activity of the studied metal-binding peptides.