The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

Molecules

Ivana Goić-Barišić¹  Nada Ilić²  Anja Golemac³  DeniseE. Strand³  Davor Juretić³  François-Xavier Pellay³  Keshi Chung³ 

[1] Department of Clinical Microbiology, Split University Hospital and Split University Medical School, 21000 Split, Croatia;Department of Physics, Faculty of Science, University of Split, 21000 Split, Croatia;Mediterranean Institute for Life Science, 21000 Split, Croatia;

关键词: antimicrobial peptides;    anticancer peptides;    therapeutic index;    design solutions;    selectivity;   

DOI  :  10.3390/molecules25153526

来源: DOAJ

【 摘 要 】

The link between the antimicrobial and anticancer activity of peptides has long been studied, and the number of peptides identified with both activities has recently increased considerably. In this work, we hypothesized that designed peptides with a wide spectrum of selective antimicrobial activity will also have anticancer activity, and tested this hypothesis with newly designed peptides. The spectrum of peptides, used as partial or full design templates, ranged from cell-penetrating peptides and putative bacteriocin to those from the simplest animals (placozoans) and the Chordata phylum (anurans). We applied custom computational tools to predict amino acid substitutions, conferring the increased product of bacteriostatic activity and selectivity. Experiments confirmed that better overall performance was achieved with respect to that of initial templates. Nine of our synthesized helical peptides had excellent bactericidal activity against both standard and multidrug-resistant bacteria. These peptides were then compared to a known anticancer peptide polybia-MP1, for their ability to kill prostate cancer cells and dermal primary fibroblasts. The therapeutic index was higher for seven of our peptides, and anticancer activity stronger for all of them. In conclusion, the peptides that we designed for selective antimicrobial activity also have promising potential for anticancer applications.

【 授权许可】

Unknown