Poster De Conférence Année : 2025

Effects of substitution of a proline residue on the cytotoxicity and antibacterial activity of the frog skin host-defence peptide, figainin 2PL

Résumé

The host-defence peptide figainin 2PL FLGTVLKLGKAIAKTVVPMLTNAMQPKQ.NH2), first isolated from skin secretions of the frog Boana platanera, inhibited growth of a range of Gram-positive and Gram-negative antibiotic resistant bacteria as well as human tumor-derived cell lines [1]. The aim of the present study was to determine the effects of increasing cationicity while maintaining amphipathicity and possibly stabilizing the helical character of the peptide on its antibacterial and cytotoxic activities. Circular dichroism studies indicated that figainin 2PL adopts a predominantly helical conformation in the membrane-mimetic solvents 10 mM dodecylphosphocholine (DPC) and 10 mM sodium dodecyl sulfate (SDS). Substitution of the Pro18 residue by either Ala, L-Lys or D-Lys had only minor effects on secondary structure but increased cytotoxic potency against A549 non-small cell lung adenocarcinoma cells, MDA-MB-231 breast adenocarcinoma cells, and HT-29 colorectal adenocarcinoma cells by between 1.5- and 3-fold (LC50 in the range 4.1 - 6.6 µM) compared with the naturally occurring peptide. However, hemolytic activity of the analogs against mouse erythrocytes increased by between 4- and 10-fold discouraging further attempts to develop the peptides into an anti-cancer agent. The growth-inhibitory potency of the [P18k] analog against the clinically relevant bacteria Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae and Pseudomonas aeruginosa was 2 - 4-fold greater (MIC in the range 1 - 8 µM) than figainin 2PL suggesting possible therapeutic potential of the peptide for development as an antimicrobial agent for topical application in cases of infection by antibiotic-resistant pathogens. [1] Conlon, J.M., Sridhar, A., Khan, D., Cunning, T.S., Delaney, J.J., Taggart, M.G., Ternan, N.G., Leprince, J., Coquet, L., Jouenne, T., Attoub, S., Mechkarska, M. Biochimie 2024, 223, 23-30

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Dates et versions

hal-05620693 , version 1 (12-05-2026)

Identifiants

  • HAL Id : hal-05620693 , version 1

Citer

J. Michael Conlon, Laure Guilhaudis, Samir Attoub, Taylor S Cunning, Jack J Delaney, et al.. Effects of substitution of a proline residue on the cytotoxicity and antibacterial activity of the frog skin host-defence peptide, figainin 2PL. French-Italian Joint Meeting GFPP, Jun 2025, Aussois, France. ⟨hal-05620693⟩
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