Calcitermin and its derivatives: novel insights into the antimicrobial activity of metal-binding peptides

Calcitermin is a 15-mer antimicrobial peptide (AMP) found in human nasal fluid and corresponding to the C-terminal domain of calgranulin C, a pro-inflammatory protein of the S100 family [1]. Preliminary studies revealed that calcitermin is a metal chelating peptide and it exhibits antifungal and antibacterial properties under acidic conditions, especially in the presence of Zn(II) and Cu(II) ions [2, 3]. Moreover, calcitermin His-to-Ala mutants – where each histidine residue is replaced with one alanine – have different metal coordination modes, resulting in significant changes of the antimicrobial properties [2]. Such bioactivity prompted us to deepen the properties of this AMP, studying the thermodynamics, structure and coordination chemistry of zinc and copper complexes with calcitermin derivatives, where the peptide structure is modified to confer higher proteolytic stability and to study the impact of metal coordination on the antimicrobial efficacy. A deep investigation of the complex formation equilibria and coordination chemistry of the formed species has been obtained by means of several techniques, including potentiometry, high-resolution mass spectrometry, UV-Vis, circular dichroism and EPR. Enzymatic stability assays provided the half-lives in human plasma of native calcitermin and its peptide derivatives and the antimicrobial activity has been tested against a representative panel of microorganisms, including Candida albicans, Escherichia coli and Staphylococcus aureus.