Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Peptidomimetics based on salivary antimicrobial peptides: fascinating intricacies of Cu(II) and Zn(II) coordination (#407)

Klaudia Szarszoń 1 , Tomasz Janek 2 , Arian Kola 3 , Fabio Zobi 4 , Robert Wieczorek 1 , Daniela Valensin 3 , Joanna Watly 1
  1. Faculty of Chemistry, University of Wrocław, Wrocław, Poland
  2. Department of Biotechnology and Food Microbiology, Wrocław University of Environmental and Life Sciences, Wrocław, Poland
  3. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
  4. Department of Chemistry, Fribourg University, Fribourg, Switzerland

MUC7, a salivary protein involved in nonimmune defense, undergoes proteolytic processing in saliva, yielding fragments with antimicrobial properties.1,2 However, their clinical potential is constrained by susceptibility to further degradation. To enhance stability, a native MUC7-derived fragment was modified using D-amino acids and a retro-inverso strategy.3

Given the known role of metal ions in enhancing activity of antimicrobial peptides4, we investigated the bioinorganic chemistry of these modified peptides with Cu(II) and Zn(II) and evaluated their antimicrobial efficacy against bacterial and fungal strains.

Various analyses including potentiometric titrations, spectroscopic studies (UV-Vis, CD, EPR, NMR), mass spectrometry - along with density functional theory (DFT) calculations suggest metal binding geometries and binding sites.

The peptides’ antimicrobial activity and metal coordination modes depend heavily on pH values. Enantiomeric substitution and retro-inverso modifications exert minimal influence on the secondary structure and antimicrobial properties of the peptides and their Cu(II) and Zn(II) complexes, however these alterations significantly influence on the thermodynamic stability of the systems.

 

Acknowledgements

The work was supported by the National Science Centre (Grant UMO-2021/41/B/ST4/02654 to J.W.)

 

 

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