Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity
<b>Background/Objectives:</b> The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles...
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MDPI AG
2025-06-01
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| author | Carolina Silva Ferreira Lívia Mara Fontes Costa Lúcio Otávio Nunes Kelton Rodrigues de Souza Giovanna Paula Araújo Evgeniy S. Salnikov Kelly Cristina Kato Helen Rodrigues Martins Adriano Monteiro de Castro Pimenta Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly |
| author_facet | Carolina Silva Ferreira Lívia Mara Fontes Costa Lúcio Otávio Nunes Kelton Rodrigues de Souza Giovanna Paula Araújo Evgeniy S. Salnikov Kelly Cristina Kato Helen Rodrigues Martins Adriano Monteiro de Castro Pimenta Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly |
| author_sort | Carolina Silva Ferreira |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. The main objective was to investigate how the site of peptide functionalization (C-terminal vs. N-terminal) affects membrane interactions and antibacterial activity. <b>Methods</b>: NP–peptide conjugates were synthesized via covalent bonding between lun-1 and alumina NP and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and solid-state <sup>13</sup>C NMR. Antibacterial activities were assessed against different Gram-positive and Gram-negative strains. Biophysical analyses, including circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and solid-state <sup>2</sup>H NMR, were employed to evaluate peptide–membrane interactions in the presence of membrane-mimetic vesicles composed of POPC:POPG (3:1) and DMPC:DMPG (3:1). <b>Results</b>: Characterization confirmed the successful formation of NP–peptide nanofilaments. Functionalization at the N-terminal significantly influenced both antibacterial activity and peptide conformation compared to C-terminal attachment. Biophysical data demonstrated stronger membrane interaction and greater membrane disruption when lun-1 was conjugated at the N-terminal. <b>Conclusions</b>: The site of peptide conjugation plays a crucial role in modulating the biological and biophysical properties of NP–lunatin-1 conjugates. C-terminal attachment of lunatin-1 retains both membrane interaction and antibacterial efficacy, making it a promising strategy for the design of peptide-based nanotherapeutics targeting resistant pathogens. |
| format | Article |
| id | doaj-art-4a928aa1cd75486fae9d9ac37c3ee824 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-4a928aa1cd75486fae9d9ac37c3ee8242025-08-20T02:47:14ZengMDPI AGPharmaceuticals1424-82472025-06-0118795210.3390/ph18070952Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial ActivityCarolina Silva Ferreira0Lívia Mara Fontes Costa1Lúcio Otávio Nunes2Kelton Rodrigues de Souza3Giovanna Paula Araújo4Evgeniy S. Salnikov5Kelly Cristina Kato6Helen Rodrigues Martins7Adriano Monteiro de Castro Pimenta8Jarbas Magalhães Resende9Burkhard Bechinger10Rodrigo Moreira Verly11Department of Chemistry, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilDepartment of Chemistry, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilDepartment of Chemistry, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilInstitute de Chimie, Université de Strasbourg/CNRS, URM7177, 67000 Strasbourg, FranceDepartment of Chemistry, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilInstitute de Chimie, Université de Strasbourg/CNRS, URM7177, 67000 Strasbourg, FranceFaculty of Pharmacy, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilFaculty of Pharmacy, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartment of Chemistry, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, BrazilInstitute de Chimie, Université de Strasbourg/CNRS, URM7177, 67000 Strasbourg, FranceDepartment of Chemistry, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina 39100-000, MG, Brazil<b>Background/Objectives:</b> The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. The main objective was to investigate how the site of peptide functionalization (C-terminal vs. N-terminal) affects membrane interactions and antibacterial activity. <b>Methods</b>: NP–peptide conjugates were synthesized via covalent bonding between lun-1 and alumina NP and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and solid-state <sup>13</sup>C NMR. Antibacterial activities were assessed against different Gram-positive and Gram-negative strains. Biophysical analyses, including circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and solid-state <sup>2</sup>H NMR, were employed to evaluate peptide–membrane interactions in the presence of membrane-mimetic vesicles composed of POPC:POPG (3:1) and DMPC:DMPG (3:1). <b>Results</b>: Characterization confirmed the successful formation of NP–peptide nanofilaments. Functionalization at the N-terminal significantly influenced both antibacterial activity and peptide conformation compared to C-terminal attachment. Biophysical data demonstrated stronger membrane interaction and greater membrane disruption when lun-1 was conjugated at the N-terminal. <b>Conclusions</b>: The site of peptide conjugation plays a crucial role in modulating the biological and biophysical properties of NP–lunatin-1 conjugates. C-terminal attachment of lunatin-1 retains both membrane interaction and antibacterial efficacy, making it a promising strategy for the design of peptide-based nanotherapeutics targeting resistant pathogens.https://www.mdpi.com/1424-8247/18/7/952nanobiomaterialsantimicrobial peptidesalumina nanoparticlesantibacterial activitylunatin-1 |
| spellingShingle | Carolina Silva Ferreira Lívia Mara Fontes Costa Lúcio Otávio Nunes Kelton Rodrigues de Souza Giovanna Paula Araújo Evgeniy S. Salnikov Kelly Cristina Kato Helen Rodrigues Martins Adriano Monteiro de Castro Pimenta Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity Pharmaceuticals nanobiomaterials antimicrobial peptides alumina nanoparticles antibacterial activity lunatin-1 |
| title | Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity |
| title_full | Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity |
| title_fullStr | Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity |
| title_full_unstemmed | Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity |
| title_short | Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity |
| title_sort | influence of peptide conjugation sites on lunatin alumina nanoparticles implications for membrane interaction and antimicrobial activity |
| topic | nanobiomaterials antimicrobial peptides alumina nanoparticles antibacterial activity lunatin-1 |
| url | https://www.mdpi.com/1424-8247/18/7/952 |
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