Solution NMR structures of the antimicrobial peptides phylloseptin-1, -2, and -3 and biological activity: The role of charges and hydrogen bonding interactions in stabilizing helix conformations

Resende, Jarbas M.; Moraes, Cléria Mendonça de; Prates, Maura V.; Cesar, Amary; Almeida, Fábio C. L.; Mundim, Nathália C.C.R.; Valente, Ana Paula; Bemquerer, Marcelo P.; Piló‐Veloso, Dorila; Bechinger, Burkhard

doi:10.1016/j.peptides.2008.06.022

Cited by 60 publications

(71 citation statements)

References 77 publications

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“…8). Therefore, contrarily to several reported cases [9, 40, 48], significantly higher structural degrees are observed for the peptides in the presence of vesicles and these results indicate that these three ocellatins show high affinity for the phospholipid bilayers.…”

Section: Resultssupporting

confidence: 50%

“…Whereas ocellatin-F1 presents pronounced disruptive properties even at very low concentrations, the dye leakage induced by ocellatin-LB1 and -LB2 seems to be more dose-dependent, which is characteristic of a cooperative mechanism that seems to demand the accumulation of peptides on the bilayer surface to effectively promote the membrane lysis [37]. These distinct mechanisms may be advantageous to the animal, since a larger choice implies in a defense mechanism that is efficient against different pathogens [38–40]. The conjoint action of these mechanisms promoted by the simultaneous secretion of different peptides can even lead to a more robust defense system [41, 42].…”

Section: Resultsmentioning

confidence: 99%

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Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Gusmao

Santos

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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BackgroundThe availability of antimicrobial peptides from several different natural sources has opened an avenue for the discovery of new biologically active molecules. To the best of our knowledge, only two peptides isolated from the frog Leptodactylus labyrinthicus, namely pentadactylin and ocellatin-F1, have shown antimicrobial activities. Therefore, in order to explore the antimicrobial potential of this species, we have investigated the biological activities and membrane interactions of three peptides isolated from the anuran skin secretion.MethodsThree peptide primary structures were determined by automated Edman degradation. These sequences were prepared by solid-phase synthesis and submitted to activity assays against gram-positive and gram-negative bacteria and against two fungal strains. The hemolytic properties of the peptides were also investigated in assays with rabbit blood erythrocytes. The conformational preferences of the peptides and their membrane interactions have been investigated by circular dichroism spectroscopy and liposome dye release assays.ResultsThe amino acid compositions of three ocellatins were determined and the sequences exhibit 100% homology for the first 22 residues (ocellatin-LB1 sequence). Ocellatin-LB2 carries an extra Asn residue and ocellatin-F1 extra Asn-Lys-Leu residues at C-terminus. Ocellatin-F1 presents a stronger antibiotic potential and a broader spectrum of activities compared to the other peptides. The membrane interactions and pore formation capacities of the peptides correlate directly with their antimicrobial activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. All peptides acquire high helical contents in membrane environments. However, ocellatin-F1 shows in average stronger helical propensities.ConclusionsThe obtained results indicate that the three extra amino acid residues at the ocellatin-F1 C-terminus play an important role in promoting stronger peptide-membrane interactions and antimicrobial properties. The extra Asn-23 residue present in ocellatin-LB2 sequence seems to decrease its antimicrobial potential and the strength of the peptide-membrane interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-017-0094-y) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Gusmao

Santos

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…3) similar to other peptide antibiotics such as phylloseptins24, magainins29 and cecropins3031. However, the hydrophobic face is interrupted by K10, which enhances the inter-chain contacts within the Htr homodimer by interacting with D5 and S9 of the opposite chain (Fig.…”

Section: Discussionmentioning

confidence: 82%

“…Htr-M shows a significant amphipathic character, where the positively charged lysine residue (K10′) represents a discontinuity within the hydrophobic region. Therefore, Htr-M is not as amphipathic as other tree-frog peptides isolated from species of the Phyllomedusinae subfamily, such as the phylloseptins and DD K2425. In the dimer, the hydrophobic residues form the core of the coiled coil structure, whereas the hydrophilic residues are exposed to the solvent molecules (Fig.…”

Section: Resultsmentioning

confidence: 98%

Structure and membrane interactions of the homodimeric antibiotic peptide homotarsinin

Verly

Resende

Eduardo.

et al. 2017

Sci Rep

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Antimicrobial peptides (AMPs) from amphibian skin are valuable template structures to find new treatments against bacterial infections. This work describes for the first time the structure and membrane interactions of a homodimeric AMP. Homotarsinin, which was found in Phyllomedusa tarsius anurans, consists of two identical cystine-linked polypeptide chains each of 24 amino acid residues. The high-resolution structures of the monomeric and dimeric peptides were determined in aqueous buffers. The dimer exhibits a tightly packed coiled coil three-dimensional structure, keeping the hydrophobic residues screened from the aqueous environment. An overall cationic surface of the dimer assures enhanced interactions with negatively charged membranes. An extensive set of biophysical data allowed us to establish structure-function correlations with antimicrobial assays against Gram-positive and Gram-negative bacteria. Although both peptides present considerable antimicrobial activity, the dimer is significantly more effective in both antibacterial and membrane biophysical assays.

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“…Although only a few of these peptides were properly tested against various microorganisms, significant differences in antimicrobial activities and target microorganism specificities have been observed between orthologous peptides, as well as paralogous peptides. For instance, PLS-H1 from Phyllomedusa hypochondrialis and phylloseptin-1 (PSN-1) from Phyllomedusa sauvagii (63% amino acid sequence identity) exhibited marked differences in their potencies to inhibit the growth of Escherichia coli (minimal inhibitory concentration, MIC = 8 µM and 80 µM, respectively) [10], [15], whereas PLS-H1 -H2, and -H3 (74% sequence identity) demonstrated almost similar activities against Gram-negative and Gram-positive bacteria (MIC ranging from 2 to 8 µM) [10], [17]. PLS-L1 from Hylomantis lemur is highly potent against the Gram-positive bacteria Staphylococcus aureus (MIC = 8 µM) [13], whereas PLS-L2 is only weakly active (MIC = 50 µM) but exhibit insulin-releasing activity [14].…”

Section: Introductionmentioning

confidence: 99%

Structure, Antimicrobial Activities and Mode of Interaction with Membranes of Bovel Phylloseptins from the Painted-Belly Leaf Frog, Phyllomedusa sauvagii

Raja

André²,

Piesse³

et al. 2013

PLoS ONE

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Transcriptomic and peptidomic analysis of skin secretions from the Painted-belly leaf frog Phyllomedusa sauvagii led to the identification of 5 novel phylloseptins (PLS-S2 to -S6) and also of phylloseptin-1 (PSN-1, here renamed PLS-S1), the only member of this family previously isolated in this frog. Synthesis and characterization of these phylloseptins revealed differences in their antimicrobial activities. PLS-S1, -S2, and -S4 (79–95% amino acid sequence identity; net charge = +2) were highly potent and cidal against Gram-positive bacteria, including multidrug resistant S. aureus strains, and killed the promastigote stage of Leishmania infantum, L. braziliensis and L. major. By contrast, PLS-S3 (95% amino acid identity with PLS-S2; net charge = +1) and -S5 (net charge = +2) were found to be almost inactive against bacteria and protozoa. PLS-S6 was not studied as this peptide was closely related to PLS-S1. Differential scanning calorimetry on anionic and zwitterionic multilamellar vesicles combined with circular dichroism spectroscopy and membrane permeabilization assays on bacterial cells indicated that PLS-S1, -S2, and -S4 are structured in an amphipathic α-helix that disrupts the acyl chain packing of anionic lipid bilayers. As a result, regions of two coexisting phases could be formed, one phase rich in peptide and the other lipid-rich. After reaching a threshold peptide concentration, the disruption of lipid packing within the bilayer may lead to local cracks and disintegration of the microbial membrane. Differences in the net charge, α-helical folding propensity, and/or degree of amphipathicity between PLS-S1, -S2 and -S4, and between PLS-S3 and -S5 appear to be responsible for their marked differences in their antimicrobial activities. In addition to the detailed characterization of novel phylloseptins from P. sauvagii, our study provides additional data on the previously isolated PLS-S1 and on the mechanism of action of phylloseptins.

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Solution NMR structures of the antimicrobial peptides phylloseptin-1, -2, and -3 and biological activity: The role of charges and hydrogen bonding interactions in stabilizing helix conformations

Cited by 60 publications

References 77 publications

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Structure and membrane interactions of the homodimeric antibiotic peptide homotarsinin

Structure, Antimicrobial Activities and Mode of Interaction with Membranes of Bovel Phylloseptins from the Painted-Belly Leaf Frog, Phyllomedusa sauvagii

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