Calcitermin (VAIALKAAHYHTHKE) is a 15-mer antimicrobial peptide found in human nasal fluid [1] which is of particular interest thanks to its metal chelating ability. Noteworthy, it exhibits improved antifungal (C. albicans) and antibacterial properties in the presence of Zn2+ and Cu2+ ions under acidic conditions, while the histidine-to-alanine mutation in position 9, 11 and 13 can modulate the activity against certain microorganisms [2]. In light of the above, we decided to extend the study to other calcitermin derivatives, where the amino acid sequence is modified to understand the impact of metal coordination on the antimicrobial activity. The new synthetised derivatives include the C- and/or N- terminal protected peptides, which could also decrease the susceptibility towards exopeptidases, the alanine-to-serine mutants (A7S, A8S and A7/8S), which are designed to stabilize copper complexes [3] and the truncated analogue Ac-AHYHTHKE-NH2 to verify if the metal coordination site of natural calcitermin can correspond to the minimum active sequence. This work is therefore aimed at characterizing the interaction of Zn2+ and Cu2+ ions with calcitermin derivatives in aqueous solutions. A deep investigation of the thermodynamic parameters of complex formation equilibria and of the 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. Financial support of the Polish National Science Centre (UMO-2020/37/N/ST4/03165) and of the COST Action CA18202, NECTAR – Network for Equilibria and Chemical Thermodynamics Advanced Research is gratefully acknowledged. [1] M. Cole, Y.-H. Kim, S. Tahk, T. Hong, P. Weis, A.J. Waring, T. Ganz, T. FEBS Lett 504 (2001) 5-10. [2] D. Bellotti, M. Toniolo, D. Dudek, A. Mikołajczyk, R. Guerrini, A. Matera-Witkiewicz, M. Remelli, M. Rowińska-Żyrek, Dalton Trans. 48 (2019) 13740-13752. [3] D. Bellotti, A. Miller, M. Rowińska-Żyrek, M. Remelli, Biomolecules 12 (2022) 121.
The impact of metal coordination on calcitermin antimicrobial properties
Denise Bellotti
;Silvia Leveraro;Maurizio Remelli
2022
Abstract
Calcitermin (VAIALKAAHYHTHKE) is a 15-mer antimicrobial peptide found in human nasal fluid [1] which is of particular interest thanks to its metal chelating ability. Noteworthy, it exhibits improved antifungal (C. albicans) and antibacterial properties in the presence of Zn2+ and Cu2+ ions under acidic conditions, while the histidine-to-alanine mutation in position 9, 11 and 13 can modulate the activity against certain microorganisms [2]. In light of the above, we decided to extend the study to other calcitermin derivatives, where the amino acid sequence is modified to understand the impact of metal coordination on the antimicrobial activity. The new synthetised derivatives include the C- and/or N- terminal protected peptides, which could also decrease the susceptibility towards exopeptidases, the alanine-to-serine mutants (A7S, A8S and A7/8S), which are designed to stabilize copper complexes [3] and the truncated analogue Ac-AHYHTHKE-NH2 to verify if the metal coordination site of natural calcitermin can correspond to the minimum active sequence. This work is therefore aimed at characterizing the interaction of Zn2+ and Cu2+ ions with calcitermin derivatives in aqueous solutions. A deep investigation of the thermodynamic parameters of complex formation equilibria and of the 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. Financial support of the Polish National Science Centre (UMO-2020/37/N/ST4/03165) and of the COST Action CA18202, NECTAR – Network for Equilibria and Chemical Thermodynamics Advanced Research is gratefully acknowledged. [1] M. Cole, Y.-H. Kim, S. Tahk, T. Hong, P. Weis, A.J. Waring, T. Ganz, T. FEBS Lett 504 (2001) 5-10. [2] D. Bellotti, M. Toniolo, D. Dudek, A. Mikołajczyk, R. Guerrini, A. Matera-Witkiewicz, M. Remelli, M. Rowińska-Żyrek, Dalton Trans. 48 (2019) 13740-13752. [3] D. Bellotti, A. Miller, M. Rowińska-Żyrek, M. Remelli, Biomolecules 12 (2022) 121.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
