{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:06:45Z","timestamp":1791083205515,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education (MOE)","award":["RG102\/20"],"award-info":[{"award-number":["RG102\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Currently, viable antibiotics available to mitigate infections caused by drug-resistant Gram-negative bacteria are highly limited. Thanatin, a 21-residue-long insect-derived antimicrobial peptide (AMP), is a promising lead molecule for the potential development of novel antibiotics. Thanatin is extremely potent, particularly against the Enterobacter group of Gram-negative pathogens, e.g., E. coli and K. pneumoniae. As a mode of action, cationic thanatin efficiently permeabilizes the LPS-outer membrane and binds to the periplasmic protein LptAm to inhibit outer membrane biogenesis. Here, we have utilized N-terminal truncated 16- and 14-residue peptide fragments of thanatin and investigated structure, activity, and selectivity with correlating modes of action. A designed 16-residue peptide containing D-Lys (dk) named VF16 (V1PIIYCNRRT-dk-KCQRF16) demonstrated killing activity in Gram-negative bacteria. The VF16 peptide did not show any detectable toxicity to the HEK 293T cell line and kidney cell line Hep G2. As a mode of action, VF16 interacted with LPS, permeabilizing the outer membrane and binding to LptAm with high affinity. Atomic-resolution structures of VF16 in complex with LPS revealed cationic and aromatic surfaces involved in outer membrane interactions and permeabilization. Further, analyses of an inactive 14-residue native thanatin peptide (IM14: IIYCNRRTGKCQRM) delineated the requirement of the \u03b2-sheet structure in activity and target interactions. Taken together, this work would pave the way for the designing of short analogs of thanatin-based antimicrobials.<\/jats:p>","DOI":"10.3390\/ijms25042122","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T11:42:05Z","timestamp":1707478925000},"page":"2122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Outer-Membrane Permeabilization, LPS Transport Inhibition: Activity, Interactions, and Structures of Thanatin Derived Antimicrobial Peptides"],"prefix":"10.3390","volume":"25","author":[{"given":"Swaleeha Jaan","family":"Abdullah","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice Tan Siu","family":"Yan","sequence":"additional","affiliation":[{"name":"A*Star Infectious Diseases Labs, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya","family":"Palanivelu","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhya Bharathi","family":"Dhanabal","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Bifani","sequence":"additional","affiliation":[{"name":"A*Star Infectious Diseases Labs, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore"},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-1937","authenticated-orcid":false,"given":"Surajit","family":"Bhattacharjya","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Antimicrobial Resistance Collaborators (2022). Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400, 2221\u20132248."},{"key":"ref_2","unstructured":"(2019). Antibiotic Resistance Threats in the United States, 2019, U.S. Department of Health and Human Services, CDC."},{"key":"ref_3","unstructured":"O\u2019Neill, J. (2016). The Review on Antimicrobial Resistance (AMR), Government of the United Kingdom."},{"key":"ref_4","unstructured":"Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 399, 629\u2013655."},{"key":"ref_5","first-page":"141","article-title":"Antimicrobial Resistance in ESKAPE Pathogens","volume":"33","author":"Forde","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1128\/AAC.05100-14","article-title":"Rapid induction of high-level carbapenem resistance in heteroresistant KPC-producing Klebsiella pneumoniae","volume":"59","author":"Nolen","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E421","DOI":"10.1111\/1469-0691.12247","article-title":"Emergence of Klebsiella pneumoniae co-producing NDM type and OXA-181 carbapenemases","volume":"19","author":"Balm","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wouters, C.L., Heydarian, N., Pusavat, J., Panlilio, H., Lam, A.K., Moen, E.L., Brennan, R.E., and Rice, C.V. (2023). Breaking membrane barriers to neutralize E. coli and K. pneumoniae virulence with PEGylated branched polyethylenimine. Biochim. Biophys. Acta (BBA)-Biomembr., 1865.","DOI":"10.1016\/j.bbamem.2023.184172"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1021\/acsinfecdis.5b00097","article-title":"Permeability Barrier of Gram-Negative Cell Envelopes and Approaches to Bypass it","volume":"1","author":"Zgurskaya","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/nrd4675","article-title":"Antibiotic resistance breakers: Can repurposed drugs fill the antibiotic discovery void?","volume":"14","author":"Brown","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1021\/acsinfecdis.8b00288","article-title":"Using Small-Molecule Adjuvants to Repurpose Azithromycin for Use against Pseudomonas aeruginosa","volume":"5","author":"Hubble","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sinha, S., Dhanabal, V.B., Manivannen, V.L., Cappiello, F., Tan, S.-M., and Bhattacharjya, S. (2022). Ultra-Short Cyclized \u03b2-Boomerang Peptides: Structures, Interactions with Lipopolysaccharide, Antibiotic Potentiator and Wound Healing. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010263"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial peptides: Application informed by evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1016\/S1473-3099(20)30327-3","article-title":"The value of antimicrobial peptides in the age of resistance","volume":"20","author":"Magana","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/s41579-021-00585-w","article-title":"Antibiofilm activity of host defence peptides: Complexity provides opportunities","volume":"19","author":"Hancock","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agadi, N., Maity, A., Jha, A.K., Chakrabarti, R., and Kumar, A. (2022). Distinct mode of membrane interaction and disintegration by diverse class of antimicrobial peptides. Biochim. Biophys. Acta (BBA)-Biomembr., 1864.","DOI":"10.1016\/j.bbamem.2022.184047"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1016\/j.jmb.2018.12.015","article-title":"Peptide Design Principles for Antimicrobial Applications","volume":"431","author":"Torres","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1021\/acsinfecdis.2c00406","article-title":"Development of Antimicrobial Peptide-Antibiotic Conjugates to Improve the Outer Membrane Permeability of Antibiotics against Gram-Negative Bacteria","volume":"8","author":"Yamauchi","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100078","DOI":"10.1016\/j.medidd.2020.100078","article-title":"Emerging peptide antibiotics with therapeutic potential","volume":"9","author":"Upert","year":"2021","journal-title":"Med. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41586-019-1665-6","article-title":"Chimeric peptidomimetic antibiotics against Gram-negative bacteria","volume":"576","author":"Luther","year":"2019","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115377","DOI":"10.1016\/j.ejmech.2023.115377","article-title":"Antimicrobial peptides: Structure, mechanism, and modification","volume":"255","author":"Chen","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nicolas, I., Bordeau, V., Bondon, A., Baudy-Floc\u2019h, M., and Felden, B. (2019). Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance. PLOS Biol., 17.","DOI":"10.1371\/journal.pbio.3000337"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bhattacharjya, S., and Straus, S.K. (2020). Design, Engineering and Discovery of Novel \u03b1-Helical and \u03b2-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165773"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Vaara, M. (2019). Polymyxins and Their Potential Next Generation as Therapeutic Antibiotics. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01689"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1021\/jm900999h","article-title":"Structure--activity relationships of polymyxin antibiotics","volume":"53","author":"Velkov","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/phar.2209","article-title":"International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)","volume":"39","author":"Tsuji","year":"2019","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gallardo-Godoy, A., Hansford, K.A., Muldoon, C., Becker, B., Elliott, A.G., Huang, J.X., Pelingon, R., Butler, M.S., Blaskovich, M.A.T., and Cooper, M.A. (2019). Structure-Function Studies of Polymyxin B Lipononapeptides. Molecules, 24.","DOI":"10.3390\/molecules24030553"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1073\/pnas.93.3.1221","article-title":"Structure-activity analysis of thanatin, a 21-residue inducible insect defense peptide with sequence homology to frog skin antimicrobial peptides","volume":"93","author":"Fehlbaum","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, J., Cha, W.H., and Lee, D.-W. (2022). Multiple Precursor Proteins of Thanatin Isoforms, an Antimicrobial Peptide Associated With the Gut Symbiont of Riptortus pedestris. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.796548"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Huynh, K., Kibrom, A., Donald, B.R., and Zhou, P. (2023). Discovery, characterization, and redesign of potent antimicrobial thanatin orthologs from Chinavia ubica and Murgantia histrionica targeting E. coli LptA. J. Struct. Biol. X, 8.","DOI":"10.1016\/j.yjsbx.2023.100091"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1038\/s41467-019-11503-3","article-title":"The Antimicrobial Peptide Thanatin Disrupts the Bacterial Outer Membrane and Inactivates the NDM-1 Metallo-\u03b2-Lactamase","volume":"10","author":"Ma","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijantimicag.2009.11.009","article-title":"Interaction of Antimicrobial Peptide S-Thanatin with Lipopolysaccharide In Vitro and in an Experimental Mouse Model of Septic Shock Caused by a Multidrug-Resistant Clinical Isolate of Escherichia coli","volume":"35","author":"Wu","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The expanding scope of antimicrobial peptide structures and their modes of action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bhattacharjya, S., Mohid, S.A., and Bhunia, A. (2022). Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094558"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14615","DOI":"10.1074\/jbc.RA119.009955","article-title":"Structural insights into the combinatorial effects of antimicrobial peptides reveal a role of aromatic-aromatic interactions in antibacterial synergism","volume":"294","author":"Ilyas","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17795","DOI":"10.1038\/s41598-017-18102-6","article-title":"Structure and interactions of a host defense antimicrobial peptide thanatin in lipopolysaccharide micelles reveal mechanism of bacterial cell agglutination","volume":"7","author":"Sinha","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/1568026615666150703121943","article-title":"NMR Structures and Interactions of Antimicrobial Peptides with Lipopolysaccharide: Connecting Structures to Functions","volume":"16","author":"Bhattacharjya","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100057","DOI":"10.1016\/j.bbadva.2022.100057","article-title":"Role of lipopolysaccharide in antimicrobial and cell penetrating peptide membrane interactions probed by deuterium NMR of whole cells","volume":"2","author":"Kumari","year":"2022","journal-title":"BBA Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18417","DOI":"10.1021\/ja1083255","article-title":"Structure, interactions, and antibacterial activities of MSI-594 derived mutant peptide MSI-594F5A in lipopolysaccharide micelles: Role of the helical hairpin conformation in outer- membrane permeabilization","volume":"132","author":"Domadia","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaau2634","DOI":"10.1126\/sciadv.aau2634","article-title":"Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in Escherichia coli","volume":"4","author":"Vetterli","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Moura, E.C., Baeta, T., Romanelli, A., Laguri, C., Martorana, A.M., Erba, E., Simorre, J.P., Sperandeo, P., and Polissi, A. (2020). Thanatin impairs lipopolysaccharide transport complex assembly by targeting LptC-LptA interaction and decreasing LptA stability. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00909"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dash, R., and Bhattacharjya, S. (2021). Thanatin: An emerging host defense antimicrobial peptide with multiple modes of action. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041522"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.resmic.2019.07.005","article-title":"The Lpt ABC transporter for lipopolysaccharide export to the cell surface","volume":"170","author":"Sperandeo","year":"2019","journal-title":"Res. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17981","DOI":"10.1074\/jbc.R117.802512","article-title":"The lipopolysaccharide transport (Lpt) machinery: A nonconventional transporter for lipopolysaccharide assembly at the outer membrane of Gram-negative bacteria","volume":"292","author":"Sperandeo","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"May, J.M., Sherman, D.J., Simpson, B.W., Ruiz, N., and Kahne, D. (2015). Lipopolysaccharide transport to the cell surface: Periplasmic transport and assembly into the outer membrane. Philos. Trans. R. Soc. B Biol. Sci., 370.","DOI":"10.1098\/rstb.2015.0027"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sperandeo, P., Martorana, A.M., Zaccaria, M., and Polissi, A. (2023). Targeting the LPS export pathway for the development of novel therapeutics. Biochim. Biophys. Acta (BBA) Mol. Cell Res., 1870.","DOI":"10.1016\/j.bbamcr.2022.119406"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41589-020-00694-2","article-title":"Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide","volume":"17","author":"Fiorentino","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sinha, S., Dhanabal, V.B., Sperandeo, P., Polissi, A., and Bhattacharjya, S. (2022). Linking dual mode of action of host defense antimicrobial peptide thanatin: Structures, lipopolysaccharide and LptAm binding of designed analogs. Biochim. Biophys. Acta (BBA)-Biomembr., 1864.","DOI":"10.1016\/j.bbamem.2021.183839"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eadg3683","DOI":"10.1126\/sciadv.adg3683","article-title":"Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug resistant Enterobacteriaceae","volume":"9","author":"Schuster","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sinha, S., Ng, W.J., and Bhattacharjya, S. (2020). NMR structure and localization of the host defense antimicrobial peptide thanatin in zwitterionic dodecylphosphocholine micelle: Implications in antimicrobial activity. Biochim. Biophys. Acta (BBA)-Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2020.183432"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1128\/AAC.26.1.48","article-title":"Compounds which increase the permeability of the Pseudomonas aeruginosa outer membrane","volume":"26","author":"Hancock","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27536","DOI":"10.1074\/jbc.M110.130955","article-title":"Escherichia coli cell surface perturbation and disruption induced by antimicrobial peptides BP100 and pepR","volume":"285","author":"Alves","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1186\/s40064-015-1476-7","article-title":"Alteration of Zeta potential and membrane permeability in bacteria: A study with cationic agents","volume":"4","author":"Halder","year":"2015","journal-title":"SpringerPlus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/ph7040482","article-title":"\u03b2-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure","volume":"7","author":"Mohanram","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1016\/j.bpj.2011.04.041","article-title":"Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides","volume":"100","author":"Kaconis","year":"2011","journal-title":"Biophys J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Heinbockel, L., Weindl, G., Correa, W., Brandenburg, J., Reiling, N., Wiesm\u00fclle, K.H., Sch\u00fcrholz, T., Gutsmann, T., de Tejada, G.M., and Mauss, K. (2021). Anti-Infective and Anti-Inflammatory Mode of Action of Peptide 19-2.5. Int J Mol Sci., 22.","DOI":"10.3390\/ijms22031465"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nehls, C., B\u00f6hling, A., Podschun, R., Schubert, S., Gr\u00f6tzinger, J., Schromm, A., Fedders, H., Leippe, M., Harder, J., and Kaconis, Y. (2020). Influence of disulfide bonds in human beta defensin-3 on its strain specific activity against Gram-negative bacteria. Biochim Biophys Acta Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2020.183273"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00232-022-00223-3","article-title":"NMR Structure and Localization of the Host Defense Peptide ThanatinM21F in Zwitterionic Dodecylphosphocholine Micelle: Implications in Antimicrobial and Hemolytic Activity","volume":"255","author":"Sinha","year":"2022","journal-title":"J. Membr. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Abdullah, S.J., Mu, Y., and Bhattacharjya, S. (2024). Structures, Interactions and Activity of the N-Terminal Truncated Variants of Antimicrobial Peptide Thanatin. Antibiotics, 13.","DOI":"10.3390\/antibiotics13010074"},{"key":"ref_61","first-page":"105","article-title":"Automated NMR protein structure calculation with CYANA","volume":"43","year":"2004","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W63","DOI":"10.1093\/nar\/gkl341","article-title":"PREDITOR: A web server for predicting protein torsion angle restraints","volume":"34","author":"Berjanskii","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/BF00228148","article-title":"AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR","volume":"8","author":"Laskowski","year":"1996","journal-title":"J. Biomol. NMR"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:58:02Z","timestamp":1760104682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,9]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042122"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042122","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,9]]}}}