{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:40:59Z","timestamp":1768084859856,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Fluoroquinolones (FQs) are broad-spectrum antibiotics largely used in the clinical practice against Gram-negative and some Gram-positive bacteria. Nevertheless, bacteria have developed several antimicrobial resistance mechanisms against such class of antibiotics. Ternary complexes of FQs, copper(II) and phenanthroline, known as metalloantibiotics, arise in an attempt to counteract an antibiotic resistance mechanism related to low membrane permeability. These metalloantibiotics seem to use an alternative influx route, independent of porins. The translocation pathways of five FQs and its metalloantibiotics were studied through biophysical experiments, allowing us to infer about the role of OmpF porin in the influx. The FQ-OmpF interaction was assessed in mimetic membrane systems differing on the lipidic composition, disclosing no interference of the lipidic composition. The drug-porin interaction revealed similar values for the association constants of FQs and metalloantibiotics with native OmpF. Therefore, OmpF mutants and specific quenchers were used to study the location-association relationship, comparing a free FQ and its metalloantibiotic. The free FQ revealed a specific association, with preference for residues on the centre of OmpF, while the metalloantibiotic showed a random interaction. Thereby, metalloantibiotics may be an alternative to pure FQs, being able to overcome some antimicrobial resistance mechanism of Gram-negative bacteria related to decreased membrane permeability.<\/jats:p>","DOI":"10.3390\/membranes11010003","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:39:29Z","timestamp":1608669569000},"page":"3","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fluoroquinolone Metalloantibiotics to Bypass Antimicrobial Resistance Mechanisms: Decreased Permeation through Porins"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-9518","authenticated-orcid":false,"given":"Mariana","family":"Ferreira","sequence":"first","affiliation":[{"name":"REQUIMTE-LAQV (Rede de Qu\u00edmica e Tecnologia\u2014Laborat\u00f3rio Associado para a Qu\u00edmica Verde), Departamento de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias, da Universidade do Porto, Rua do Campo Alegre, s\/n, 4169-007 Porto, Portugal"}]},{"given":"Carla F.","family":"Sousa","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV (Rede de Qu\u00edmica e Tecnologia\u2014Laborat\u00f3rio Associado para a Qu\u00edmica Verde), Departamento de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias, da Universidade do Porto, Rua do Campo Alegre, s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-6853","authenticated-orcid":false,"given":"Paula","family":"Gameiro","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV (Rede de Qu\u00edmica e Tecnologia\u2014Laborat\u00f3rio Associado para a Qu\u00edmica Verde), Departamento de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias, da Universidade do Porto, Rua do Campo Alegre, s\/n, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, November 25). Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics. Available online: https:\/\/www.who.int\/news-room\/detail\/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed."},{"key":"ref_2","first-page":"173","article-title":"Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer","volume":"7","author":"Penders","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_3","unstructured":"ECDC (2017). Antimicrobial Resistance Surveillance in Europe 2015. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net), European Centre for Disease Prevention and Control (ECDC)."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1128\/CMR.00043-12","article-title":"Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance","volume":"25","author":"Hancock","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jconrel.2016.10.018","article-title":"The bacterial cell envelope as delimiter of anti-infective bioavailability\u2014An in vitro permeation model of the Gram-negative bacterial inner membrane","volume":"243","author":"Graef","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bbamem.2008.08.023","article-title":"Lipid domains in bacterial membranes and the action of antimicrobial agents","volume":"1788","author":"Epand","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a000414","DOI":"10.1101\/cshperspect.a000414","article-title":"The Bacterial Cell Envelope","volume":"2","author":"Silhavy","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bbapap.2008.11.005","article-title":"Outer membrane permeability and antibiotic resistance","volume":"1794","author":"Delcour","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1365-2958.2000.01983.x","article-title":"Structure and function of bacterial outer membrane proteins: Barrels in a nutshell","volume":"37","author":"Koebnik","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.bbamem.2015.10.018","article-title":"Molecular mechanisms of membrane targeting antibiotics","volume":"1858","author":"Epand","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.2174\/1874285801307010022","article-title":"Structure, Function and Regulation of Outer Membrane Proteins Involved in Drug Transport in Enterobactericeae: The OmpF\/C\u2014TolC Case","volume":"7","author":"Masi","year":"2013","journal-title":"Open Microbiol. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20150023","DOI":"10.1098\/rstb.2015.0023","article-title":"Outer membrane protein biogenesis in Gram-negative bacteria","volume":"370","author":"Rollauer","year":"2015","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.str.2012.10.014","article-title":"The Binding of Antibiotics in OmpF Porin","volume":"21","author":"Ziervogel","year":"2013","journal-title":"Structure"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1177\/1087057109357791","article-title":"Permeation of Antibiotics through Escherichia coli OmpF and OmpC Porins","volume":"15","author":"Mahendran","year":"2010","journal-title":"J. Biomol. Screen."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg212","article-title":"Development of the quinolones","volume":"51","author":"Andersson","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","first-page":"455","article-title":"Quinolones: A comprehensive review","volume":"65","author":"Oliphant","year":"2002","journal-title":"Am. Fam. Physician"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0924-8579(00)00192-8","article-title":"The fluoroquinolone antibacterials: Past, present and future perspectives","volume":"16","author":"Appelbaum","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17001","DOI":"10.1038\/nmicrobiol.2017.1","article-title":"Mechanisms of envelope permeability and antibiotic influx and efflux in Gram-negative bacteria","volume":"2","author":"Masi","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lou, H., Chen, M., Black, S.S., Bushell, S.R., Ceccarelli, M., Mach, T., Beis, K., Low, A.S., Bamford, V.A., and Booth, I.R. (2011). Altered Antibiotic Transport in OmpC Mutants Isolated from a Series of Clinical Strains of Multi-Drug Resistant E. coli. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025825"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1021\/jp911485k","article-title":"Molecular Basis of Enrofloxacin Translocation through OmpF, an Outer Membrane Channel of Escherichia coli\u2014When Binding Does Not Imply Translocation","volume":"114","author":"Mahendran","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1021\/bi5000564","article-title":"Mechanism of Quinolone Action and Resistance","volume":"53","author":"Aldred","year":"2014","journal-title":"Biochemisty"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1751-7915.2008.00063.x","article-title":"Mechanism of action of and resistance to quinolones","volume":"2","author":"Madurga","year":"2009","journal-title":"Microb. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jinorgbio.2014.05.007","article-title":"Fluoroquinolone\u2013metal complexes: A route to counteract bacterial resistance?","volume":"138","author":"Feio","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jinorgbio.2010.03.017","article-title":"Solution and biological behaviour of enrofloxacin metalloantibiotics: A route to counteract bacterial resistance?","volume":"104","author":"Saraiva","year":"2010","journal-title":"J. Inorg. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jinorgbio.2012.02.003","article-title":"Synthesis, characterization and antibacterial studies of a copper(II) levofloxacin ternary complex","volume":"110","author":"Sousa","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jinorgbio.2013.10.013","article-title":"Synthesis, characterization and antibacterial studies of a copper(II) lomefloxacin ternary complex","volume":"131","author":"Fernandes","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ijpharm.2006.10.035","article-title":"Solution studies on binary and ternary complexes of copper(II) with some fluoroquinolones and 1,10-phenanthroline: Antimicrobial activity of ternary metalloantibiotics","volume":"334","author":"Gameiro","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tvjl.2005.07.010","article-title":"Pharmacology of the fluoroquinolones: A perspective for the use in domestic animals","volume":"172","author":"Martinez","year":"2006","journal-title":"Vet. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0010-8545(02)00027-9","article-title":"The interactions of metal ions with quinolone antibacterial agents","volume":"232","author":"Turel","year":"2002","journal-title":"Co-Ord. Chem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.poly.2008.09.018","article-title":"Synthesis, structure and biological properties of several binary and ternary complexes of copper(II) with ciprofloxacin and 1,10 phenanthroline","volume":"28","author":"Ortiz","year":"2009","journal-title":"Polyhedron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12269","DOI":"10.1016\/S0021-9258(19)86305-6","article-title":"Oxygen-dependent cleavage of DNA by the 1,10-phenanthroline. cuprous complex. Inhibition of Escherichia coli DNA polymerase I","volume":"254","author":"Sigman","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/1439-7633(20011001)2:10<735::AID-CBIC735>3.0.CO;2-#","article-title":"Artificial Nucleases","volume":"2","author":"Chen","year":"2001","journal-title":"Chembiochem"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7147","DOI":"10.1073\/pnas.83.19.7147","article-title":"Nuclease activity of 1,10-phenanthroline-copper: Sequence-specific targeting","volume":"83","author":"Chen","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1134\/S1070328409020018","article-title":"The complexes of metal ions with fluoroquinolones","volume":"35","author":"Serafin","year":"2009","journal-title":"Russ. J. Co-Ord. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10009","DOI":"10.1039\/C6RA26466B","article-title":"The binding of free and copper-complexed fluoroquinolones to OmpF porins: An experimental and molecular docking study","volume":"7","author":"Sousa","year":"2017","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00232-014-9749-6","article-title":"Ciprofloxacin Metalloantibiotic: An Effective Antibiotic with an Influx Route Strongly Dependent on Lipid Interaction?","volume":"248","author":"Ferreira","year":"2014","journal-title":"J. Membr. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ijpharm.2015.09.037","article-title":"Interactions of a non-fluorescent fluoroquinolone with biological membrane models: A multi-technique approach","volume":"495","author":"Sousa","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/cbdd.12071","article-title":"A New Approach to Counteract Bacteria Resistance: A Comparative Study Between Moxifloxacin and a New Moxifloxacin Derivative in Different Model Systems of Bacterial Membrane","volume":"81","author":"Lopes","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00232-011-9368-4","article-title":"New Insights into the Translocation Route of Enrofloxacin and Its Metalloantibiotics","volume":"241","author":"Ribeiro","year":"2011","journal-title":"J. Membr. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1562\/0031-8655(2001)0730014DBFTOT2.0.CO2","article-title":"Determination by Fluorimetric Titration of the Ionization Constants of Ciprofloxacin in Solution and in the Presence of Liposomes","volume":"73","author":"Berlanga","year":"2007","journal-title":"Photochem. Photobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0939-6411(02)00018-8","article-title":"Determination of lipophilicity of two quinolone antibacterials, ciprofloxacin and grepafloxacin, in the protonation equilibrium","volume":"54","author":"Sun","year":"2002","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejps.2011.06.009","article-title":"Lipophilicity of zwitterions and related species: A new insight","volume":"44","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jinorgbio.2007.01.009","article-title":"Synthesis, structure, and nuclease properties of several binary and ternary complexes of copper(II) with norfloxacin and 1,10 phenantroline","volume":"101","author":"Ruiz","year":"2007","journal-title":"J. Inorg. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.jinorgbio.2006.03.013","article-title":"Neutral and cationic mononuclear copper(II) complexes with enrofloxacin: Structure and biological activity","volume":"100","author":"Efthimiadou","year":"2006","journal-title":"J. Inorg. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0003-2697(71)90443-X","article-title":"An accurate and convenient organic phosphorus assay","volume":"39","author":"McClare","year":"1971","journal-title":"Anal. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/S0021-9258(18)70226-3","article-title":"Phosphorus assay in column chromatography","volume":"234","author":"Bartlett","year":"1959","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ab.2015.03.026","article-title":"A fast way to track functional OmpF reconstitution in liposomes: Escherichia coli total lipid extract","volume":"479","author":"Lopes","year":"2015","journal-title":"Anal. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0003-2697(88)90383-1","article-title":"Investigation of the bicinchoninic acid protein assay: Identification of the groups responsible for color formation","volume":"175","author":"Wiechelman","year":"1988","journal-title":"Anal. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurement of protein using bicinchoninic acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1021\/es0155276","article-title":"Fluorescence Inner-Filtering Correction for Determining the Humification Index of Dissolved Organic Matter","volume":"36","author":"Ohno","year":"2002","journal-title":"Environ. Sci. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1021\/es0000293","article-title":"Effect of Organic Amendments on Herbicide Sorption as Related to the Nature of the Dissolved Organic Matter","volume":"34","author":"Cox","year":"2000","journal-title":"Environ. Sci. Technol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13301","DOI":"10.1021\/ja803188c","article-title":"Facilitated Permeation of Antibiotics across Membrane Channels\u2014Interaction of the Quinolone Moxifloxacin with the OmpF Channel","volume":"130","author":"Mach","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1021\/ed070p425","article-title":"Ribonuclease T1 and alcohol dehydrogenase fluorescence quenching by acrylamide: A laboratory experiment for undergraduate students","volume":"70","author":"Coutinho","year":"1993","journal-title":"J. Chem. Educ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00232-008-9152-2","article-title":"Fluorescence Quenching as a Tool to Investigate Quinolone Antibiotic Interactions with Bacterial Protein OmpF","volume":"227","author":"Neves","year":"2009","journal-title":"J. Membr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bpc.2004.08.004","article-title":"Interaction between quinolones antibiotics and bacterial outer membrane porin OmpF","volume":"113","author":"Neves","year":"2005","journal-title":"Biophys. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lakowicz, J.R. (2006). Principles of Fluorescence Spectroscopy, Springer Science & Business Media LLC. [4th ed.].","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.aca.2006.09.067","article-title":"Correction of inner-filter effect in fluorescence excitation-emission matrix spectrometry using Raman scatter","volume":"583","author":"Larsson","year":"2007","journal-title":"Anal. Chim. Acta"},{"key":"ref_58","first-page":"341","article-title":"Assessment of inner filter effect corrections in fluorimetry","volume":"340","author":"Puchalski","year":"1991","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00232-011-9414-2","article-title":"Liposomes as a Model for the Biological Membrane: Studies on Daunorubicin Bilayer Interaction","volume":"245","author":"Matos","year":"2012","journal-title":"J. Membr. Biol."},{"key":"ref_60","first-page":"1049","article-title":"Validity and applicability of membrane model systems for studying interactions of peripheral membrane proteins with lipids","volume":"1841","author":"Czogalla","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1590\/S0100-879X2002000700001","article-title":"Membrane proteins: Functional and structural studies using reconstituted proteoliposomes and 2-D crystals","volume":"35","author":"Rigaud","year":"2002","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/femsre\/fuv008","article-title":"Bacterial membrane lipids: Diversity in structures and pathways","volume":"40","author":"Sohlenkamp","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1016\/j.bbamem.2007.07.016","article-title":"Ciprofloxacin interactions with bacterial protein OmpF: Modelling of FRET from a multi-tryptophan protein trimer","volume":"1768","author":"Fernandes","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"843","DOI":"10.2174\/138920312804871120","article-title":"Microbe-Host Interactions: Structure and Role of Gram-Negative Bacterial Porins","volume":"13","author":"Galdiero","year":"2012","journal-title":"Curr. Protein Pept. Sci."}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/1\/3\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:21Z","timestamp":1760179701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/1\/3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["membranes11010003"],"URL":"https:\/\/doi.org\/10.3390\/membranes11010003","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,22]]}}}