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Methods: To understand the mechanisms behind these enhanced properties, comparative analyses of the structural, topological, biophysical, and thermodynamic aspects of the interactions between each peptide and phospholipid bilayers were evaluated. Both peptides were isotopically labeled with 2H3-Ala and 15N-Leu to facilitate structural studies via NMR spectroscopy. Results: Circular dichroism and solid-state NMR analyses revealed that, while both peptides adopt \u03b1-helical conformations in membrane mimetic environments, LyeTx I-b exhibits a more amphipathic and extended helical structure, which correlates with its enhanced membrane interaction. The thermodynamic properties of the peptide\u2013membrane interactions were quantitatively evaluated in the presence of phospholipid bilayers using ITC and DSC, highlighting a greater propensity of LyeTx I-b to disrupt lipid vesicles. Calcein release studies reveal that both peptides cause vesicle disruption, although DLS measurements and TEM imaging indicate distinct effects on phospholipid vesicle organization. While LyeTx I-b permeabilizes anionic membrane retaining the vesicle integrity, LyeTx I promotes significant vesicle agglutination. Furthermore, DSC and calcein release assays indicate that LyeTx I-b exhibits significantly lower cytotoxicity toward eukaryotic membranes compared to LyeTx I, suggesting greater selectivity for bacterial membranes. Conclusions: Our findings provide insights into the structural and functional modifications that enhance the antimicrobial and therapeutic potential of LyeTx I-b, offering valuable guidance for the design of novel peptides targeting resistant bacterial infections and cancer.<\/jats:p>","DOI":"10.3390\/antibiotics14010066","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T06:25:54Z","timestamp":1736490354000},"page":"66","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative Structural and Biophysical Investigation of Lycosa erythrognatha Toxin I (LyeTx I) and Its Analog LyeTx I-b"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-5966","authenticated-orcid":false,"given":"Amanda Neves","family":"de Souza","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil"},{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele de Azevedo","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-2633","authenticated-orcid":false,"given":"L\u00facio Ot\u00e1vio","family":"Nunes","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Aisenbrey","sequence":"additional","affiliation":[{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5843-4125","authenticated-orcid":false,"given":"Evgeniy","family":"Salnikov","sequence":"additional","affiliation":[{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelton Rodrigues","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil"},{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Saad","sequence":"additional","affiliation":[{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-4032","authenticated-orcid":false,"given":"Maria Elena","family":"de Lima","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu em Medicina e Biomedicina, Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Belo Horizonte 30150-221, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-7312","authenticated-orcid":false,"given":"Jarbas Magalh\u00e3es","family":"Resende","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-6073","authenticated-orcid":false,"given":"Burkhard","family":"Bechinger","sequence":"additional","affiliation":[{"name":"Institut de Chimie, Universit\u00e9 de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, France"},{"name":"Institut Universitaire de France, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-6862","authenticated-orcid":false,"given":"Rodrigo Moreira","family":"Verly","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Akbarian, M., Khani, A., Eghbalpour, S., and Uversky, V.N. (2022). Bioactive Peptides: Synthesis, Sources, Applications, and Proposed Mechanisms of Action. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031445"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00726-009-0385-x","article-title":"LyeTx I, a potent antimicrobial peptide from the venom of the spider Lycosa erythrognatha","volume":"39","author":"Santos","year":"2010","journal-title":"Amino Acids"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/299371a0","article-title":"The helical hydrophobic moment: A measure of the amphiphilicity of a helix","volume":"299","author":"Eisenberg","year":"1982","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Reis, P.V.M., Boff, D., Verly, R.M., Melo-Braga, M.N., Cort\u00e9s, M.E., Santos, D.M., Pimenta, A.M.D.C., Amaral, F.A., Resende, J.M., and De Lima, M.E. (2018). LyeTxI-b, a Synthetic Peptide Derived from Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity In Vitro and In Vivo. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00667"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00726-018-2678-4","article-title":"The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells","volume":"51","author":"Gomes","year":"2019","journal-title":"Amino Acids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"da Silva, C.N., da Silva, F.R., Dourado, L.F.N., dos Reis, P.V.M., Silva, R.O., da Costa, B.L., Nunes, P.S., Amaral, F.A., dos Santos, V.L., and de Lima, M.E. (2019). A New Topical Eye Drop Containing LyeTxI-b, a Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis. Toxins, 11.","DOI":"10.3390\/toxins11040203"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1093\/bioinformatics\/btn392","article-title":"HELIQUEST: A web server to screen sequences with specific alpha-helical properties","volume":"24","author":"Gautier","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1021\/bi952000v","article-title":"Poly(ethylene glycol)\u2212Lipid Conjugates Regulate the Calcium-Induced Fusion of Liposomes Composed of Phosphatidylethanolamine and Phosphatidylserine","volume":"35","author":"Holland","year":"1996","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.bbamem.2007.04.016","article-title":"Aggregation and hemi-fusion of anionic vesicles induced by the antimicrobial peptide cryptdin-4","volume":"1768","author":"Cummings","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1039\/D2NA00464J","article-title":"Leaky membrane fusion: An ambivalent effect induced by antimicrobial polycations","volume":"4","author":"Shi","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_11","first-page":"186","article-title":"Determination of critical micelle concentration (Cmc) of sodium dodecyl sulfate (SDS) and the effect of low concentration of pyrene on its Cmc using ORIGIN software","volume":"30","author":"Khan","year":"2008","journal-title":"J. Chem. Soc. Pak."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1051\/epn\/19861701011","article-title":"NMR with Proteins and Nucleic Acids","volume":"17","year":"1986","journal-title":"Eur. News"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1021\/bi049409h","article-title":"Tilt and Rotational Pitch Angle of Membrane-Inserted Polypeptides from Combined 15N and 2H Solid-State NMR Spectroscopy","volume":"43","author":"Aisenbrey","year":"2004","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/0006-291X(74)90318-0","article-title":"A study of mobility and order in model membranes using 2H NMR relaxation rates and quadrupole splittings of specifically deuterated lipids","volume":"60","author":"Stockton","year":"1974","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.drudis.2012.01.023","article-title":"How to conduct and interpret ITC experiments accurately for cyclodextrin\u2013guest interactions","volume":"17","author":"Bouchemal","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lewis, E.A., and Murphy, K.P. (2005). Isothermal Titration Calorimetry, Humana.","DOI":"10.1385\/1-59259-912-5:001"},{"key":"ref_17","unstructured":"Malvern Instruments Ltd. (2013). Zetasizer Nano Series User Manual, Malvern Instruments Ltd."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.18388\/abp.2005_3455","article-title":"Circular dichroism and aggregation studies of amyloid beta (11-8) fragment and its variants","volume":"52","author":"Juszczyk","year":"2005","journal-title":"Acta Biochim. Pol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3938","DOI":"10.1111\/j.1742-4658.2005.04812.x","article-title":"The Alzheimer \u03b2-peptide shows temperature-dependent transitions between left-handed 31-helix, \u03b2-strand and random coil secondary structures","volume":"272","author":"Danielsson","year":"2005","journal-title":"FEBS J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.1021\/ja991167z","article-title":"Reversible Random Coil to \u03b2-Sheet Transition and the Early Stage of Aggregation of the A\u03b2(12\u221228) Fragment from the Alzheimer Peptide","volume":"122","author":"Jarvet","year":"2000","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1002\/bip.360321209","article-title":"\u03b1-helix to random coil transitions: Determination of peptide concentration from the CD at the isodichroic point","volume":"32","author":"Holtzer","year":"1992","journal-title":"Biopolymers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1016\/j.bbamem.2012.02.027","article-title":"Lipid shape is a key factor for membrane interactions of amphipathic helical peptides","volume":"1818","author":"Strandberg","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bischoff, N., Wimberger, S., Maresca, M., and Brakebusch, C. (2020). Improving Precise CRISPR Genome Editing by Small Molecules: Is there a Magic Potion?. Cells, 9.","DOI":"10.3390\/cells9051318"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.bbamem.2017.12.018","article-title":"Effect of N-terminal acetylation on lytic activity and lipid-packing perturbation induced in model membranes by a mastoparan-like peptide","volume":"1860","author":"Alvares","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/pmic.201000397","article-title":"Targeted large-scale analysis of protein acetylation","volume":"11","author":"Mischerikow","year":"2011","journal-title":"Proteomics"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Raja, Z., Andr\u00e9, S., Piesse, C., Sereno, D., Nicolas, P., Foulon, T., Oury, B., and Ladram, A. (2013). Structure, Antimicrobial Activities and Mode of Interaction with Membranes of Bovel Phylloseptins from the Painted-Belly Leaf Frog, Phyllomedusa sauvagii. PLoS ONE, 8.","DOI":"10.1371\/annotation\/dbb3e614-dc4c-40dd-b9e0-37787ae6b150"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4103\/0975-7406.76467","article-title":"C- and N-truncated antimicrobial peptides from LFampin 265\u2013284: Biophysical versus microbiology results","volume":"3","author":"Bastos","year":"2011","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00726-021-03029-0","article-title":"Membrane interactions of Ocellatins. Where do antimicrobial gaps stem from?","volume":"53","author":"Oliveira","year":"2021","journal-title":"Amino Acids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10989-014-9430-z","article-title":"Cationic Antimicrobial Peptides Cytotoxicity on Mammalian Cells: An Analysis Using Therapeutic Index Integrative Concept","volume":"21","author":"Bacalum","year":"2015","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.molliq.2015.06.025","article-title":"Exploring the mechanism of fluorescence quenching in two biologically active boronic acid derivatives using Stern-Volmer kinetics","volume":"209","author":"Geethanjali","year":"2015","journal-title":"J. Mol. Liq."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1110\/ps.03258404","article-title":"On the analysis of membrane protein circular dichroism spectra","volume":"13","author":"Sreerama","year":"2004","journal-title":"Protein Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2433","DOI":"10.21769\/BioProtoc.2433","article-title":"Liposome Disruption Assay to Examine Lytic Properties of Biomolecules","volume":"7","author":"Jimah","year":"2017","journal-title":"Bio-Protocol"},{"key":"ref_33","unstructured":"(2024, May 31). Determination of Total Phosphorus|Avanti Polar Lipids (EN-US). Available online: https:\/\/avantilipids.com\/tech-support\/analytical-procedures\/determination-of-total-phosphorus."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0022-2836(83)80143-0","article-title":"Conformation of glucagon in a lipid-water interphase by 1H nuclear magnetic resonance","volume":"169","author":"Braun","year":"1983","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1080\/00268978900102331","article-title":"Broadband homonuclear cross polarization in 2D N.M.R. using DIPSI-2","volume":"68","author":"Rucker","year":"1989","journal-title":"Mol. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/mrc.1260310315","article-title":"Gradient selection in inverse heteronuclear correlation spectroscopy","volume":"31","author":"Willker","year":"1993","journal-title":"Magn. Reson. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: A multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J. Biomol. NMR"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/BF00404272","article-title":"NMR View: A computer program for the visualization and analysis of NMR data","volume":"4","author":"Johnson","year":"1994","journal-title":"J. Biomol. NMR"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/pro.5560010606","article-title":"The solution structure of eglin c based on measurements of many NOEs and coupling constants and its comparison with X-ray structures","volume":"1","author":"Hyberts","year":"1992","journal-title":"Protein Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10858-009-9333-z","article-title":"TALOS+: A hybrid method for predicting protein backbone torsion angles from NMR chemical shifts","volume":"44","author":"Shen","year":"2009","journal-title":"J. Biomol. NMR"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/prot.340190403","article-title":"Torsion angle dynamics: Reduced variable conformational sampling enhances crystallographic structure refinement","volume":"19","author":"Rice","year":"1994","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pnmrs.2005.10.001","article-title":"Using Xplor\u2013NIH for NMR molecular structure determination","volume":"48","author":"Schwieters","year":"2006","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0263-7855(96)00009-4","article-title":"MOLMOL: A program for display and analysis of macromolecular structures","volume":"14","author":"Koradi","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/psc.2656","article-title":"On the design of supramolecular assemblies made of peptides and lipid bilayers","volume":"20","author":"Koumkoua","year":"2014","journal-title":"J. Pept. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-60761-594-1_14","article-title":"Solid-State NMR Investigations of Membrane-Associated Antimicrobial Peptides","volume":"618","author":"Aisenbrey","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0022-2364(83)90190-7","article-title":"Obtaining high-fidelity powder spectra in anisotropic media: Phase-cycled Hahn echo spectroscopy","volume":"52","author":"Rance","year":"1983","journal-title":"J. Magn. Reson. (1969)"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Munhoz, V.H., Ferreira, C.S., Nunes, L.O., Santos, T.L., Aisenbrey, C., Ad\u00e3o, R., de Carvalho Alc\u00e2ntara, A.F., de Magalh\u00e3es, M.T., Pil\u00f3-Veloso, D., and Resende, J.M. (2021). Epimers l- and d-Phenylseptin: How the relative stereochemistry affects the peptide-membrane interactions. Biochim. Biophys. Acta (BBA)\u2014Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2021.183708"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/66\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:26:12Z","timestamp":1759919172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/66"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["antibiotics14010066"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14010066","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}