Antibiotic resistance remains one of the most pressing global health challenges, calling for the development of alternative antimicrobial strategies.1 The presented research introduces a new class of antimicrobial compounds – peptidomimetics inspired by natural salivary peptides, designed for enhanced stability and efficacy through strategic chemical modifications.
Human salivary antimicrobial peptides (AMPs), such as histatins, chemokines, cathelicidin, defensins, and mucins, possess innate infection-fighting capabilities.2-4 However, their therapeutic potential is limited due to poor enzymatic stability. To overcome this limitation, a dual-modification strategy was employed: incorporation of D-amino acids and sequence inversion (retro-inverso strategy) to improve metabolic stability, along with coordination to essential metal ions, such as Zn(II) and Cu(II), to boost antimicrobial activity.
These modifications result in stable, long-lasting metal–peptide complexes with strong activity against a broad spectrum of pathogens. Preliminary results show a clear correlation between metal-binding properties, structural modifications, and biological function.5 This research bridges coordination chemistry and peptide science, offering new insights into metal–peptide interactions and paving the way for novel therapeutic approaches.
The expected outcome of the ongoing studies is a new generation of proteolytically stable, metal-coordinated peptidomimetics with broad biomedical potential. Beyond the treatment of infectious diseases, the findings may also contribute to other areas of peptide-based drug development, helping shape the future of antimicrobial therapy.
Acknowledgements
J.W. acknowledges the National Science Centre (UMO-2021/41/B/ST4/02654) and NAWA Canaletto grant (BPN/BIT/2024/1/00057) for financial support.