Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity
In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH<sub>2</sub>), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/4/542 |
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| author | Gustavo Penteado Battesini Carretero Greice Kelle Viegas Saraiva Magali Aparecida Rodrigues Sumika Kiyota Marcelo Porto Bemquerer Hernan Chaimovich Iolanda Midea Cuccovia |
| author_facet | Gustavo Penteado Battesini Carretero Greice Kelle Viegas Saraiva Magali Aparecida Rodrigues Sumika Kiyota Marcelo Porto Bemquerer Hernan Chaimovich Iolanda Midea Cuccovia |
| author_sort | Gustavo Penteado Battesini Carretero |
| collection | DOAJ |
| description | In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH<sub>2</sub>), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH<sub>2</sub>). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm. |
| first_indexed | 2024-03-10T12:31:15Z |
| format | Article |
| id | doaj.art-c1a3ba403ca8481b9ad776d3dcf7d521 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T12:31:15Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c1a3ba403ca8481b9ad776d3dcf7d5212023-11-21T14:41:05ZengMDPI AGBiomolecules2218-273X2021-04-0111454210.3390/biom11040542Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial ActivityGustavo Penteado Battesini Carretero0Greice Kelle Viegas Saraiva1Magali Aparecida Rodrigues2Sumika Kiyota3Marcelo Porto Bemquerer4Hernan Chaimovich5Iolanda Midea Cuccovia6Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508000, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508000, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508000, BrazilLaboratório de Bioquímica de Proteínas e Peptídeos, Instituto Biológico, São Paulo, SP 04014002, BrazilEmbrapa Recursos Genéticos e Biotecnologia, Parque Estação Biológica, Empresa Brasileira de Pesquisa Agropecuária, Brasília, DF 70770900, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508000, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508000, BrazilIn a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH<sub>2</sub>), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH<sub>2</sub>). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.https://www.mdpi.com/2218-273X/11/4/542antimicrobial peptideBP100model membranesspectroscopycalorimetrybiological activity |
| spellingShingle | Gustavo Penteado Battesini Carretero Greice Kelle Viegas Saraiva Magali Aparecida Rodrigues Sumika Kiyota Marcelo Porto Bemquerer Hernan Chaimovich Iolanda Midea Cuccovia Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity Biomolecules antimicrobial peptide BP100 model membranes spectroscopy calorimetry biological activity |
| title | Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity |
| title_full | Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity |
| title_fullStr | Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity |
| title_full_unstemmed | Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity |
| title_short | Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity |
| title_sort | naphthalimide containing bp100 leads to higher model membranes interactions and antimicrobial activity |
| topic | antimicrobial peptide BP100 model membranes spectroscopy calorimetry biological activity |
| url | https://www.mdpi.com/2218-273X/11/4/542 |
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