Interaction of synthetic antimicrobial peptides of the Hylin a1 family with models of eukaryotic structures: Zwitterionic membranes and DNA.
| Autor: | Vignoli Muniz GS; Instituto de Física, Universidade de São Paulo, SP, Brazil., De la Torre LI; Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil., Duarte EL; Instituto de Física, Universidade de São Paulo, SP, Brazil., Lorenzón EN; Unidade Acadêmica Especial Ciências da Saúde, Universidade Federal de Jataí, Jataí, GO, Brazil., Cilli EM; Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brazil., Balan A; Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil., Lamy MT; Instituto de Física, Universidade de São Paulo, SP, Brazil. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Biochemistry and biophysics reports [Biochem Biophys Rep] 2020 Nov 03; Vol. 24, pp. 100827. Date of Electronic Publication: 2020 Nov 03 (Print Publication: 2020). |
| DOI: | 10.1016/j.bbrep.2020.100827 |
| Abstrakt: | Antimicrobial peptides (AMPs) have been appointed as a possible alternative to traditional antibiotics in face of pathogens increasing resistance to conventional drugs. Hylin a1 (IFGAILPLALGALKNLIK), an AMP extracted from the skin secretion of a South American frog, Hypsiboas albopunctatus , was found to show a strong cytotoxicity against bacteria and fungus, but also a considerable hemolytic action. Considering the toxicity of the peptide in eukaryotic cells, this work focuses on investigating the effects of the interaction of the Hylin a1 analogues W 6 Hya1, D 0 W 6 Hya1 and K 0 W 6 Hya1 with models of eukaryotic structures, namely zwitterionic liposomes of dipalmitoyl phosphatidylcholine (DPPC) and calf-thymus DNA (CT DNA). Through intrinsic Trp fluorescence we determined that the peptide affinity for fluid DPPC bilayers follows the decreasing order: D 0 W 6 Hya1 (+2) > W 6 Hya1 (+3) » K 0 W 6 Hya1 (+4). Fluorescence data also indicate that the Trp residue in the more positively charged peptide, K 0 W 6 Hya1, is less deep in the bilayer than the residue in the other two peptides. This finding is supported by differential scanning calorimetry (DSC) data, which shows that both D 0 W 6 Hya1 and W 6 Hya1 disturb DPPC gel-fluid transition slightly more effectively than K 0 W 6 Hya1. DPPC DSC profiles are homogeneously disturbed by the three peptides, probably related to peptide-membrane diffusion. Surprisingly, the peptide that displays the lowest affinity for PC membranes and is located at the more superficial position in the bilayer, K 0 W 6 Hya1, is the most efficient in causing formation of pores on the membrane, as attested by carboxyfluorescein leakage assays. The three peptides were found to interact with CT DNA, with a deep penetration of the Trp residue into hydrophobic pockets of the double helix, as indicated by the significant blue shift on the Trp fluorescence, and the displacement of DNA-bound ethidium bromide by the peptides. The experiments of DNA electrophoresis confirm that Hylin peptides bind DNA in a concentration-dependent manner, inducing complete DNA retardation at the relative AMP/plasmid DNA weight ratio of ~17. These findings could help to better understand the AMPs toxic effects on eukaryotic cells, thus contributing to the design of healthier therapeutic agents. Competing Interests: There is no conflict of interest among authors. (© 2020 The Authors.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|