α-Helical Structure of Antimicrobial Peptides Enhances Their Activity through Molecular Surface Signatures
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| Titel: | α-Helical Structure of Antimicrobial Peptides Enhances Their Activity through Molecular Surface Signatures |
|---|---|
| Autoren: | Michael Quagliata, Joshua Grabeck, Kathrin König, Anna Maria Papini, Paolo Rovero, Ines Neundorf, Daniel Friedrich |
| Quelle: | Biochemistry. 64:3311-3321 |
| Verlagsinformationen: | American Chemical Society (ACS), 2025. |
| Publikationsjahr: | 2025 |
| Schlagwörter: | Antimicrobial activity, Chemical structure, Hydrophobicity, Monomers, Peptides and proteins |
| Beschreibung: | The increase in antibacterial resistance is one of the greatest challenges in modern medicine, driving an urgent need to develop new drugs to combat resistant pathogens. Peptides represent a promising class of molecules that can be efficiently designed to exhibit high antimicrobial efficacy. Recently, we have highlighted how prestructuring by a triazolyl-bridge significantly enhances the activity of an antimicrobial peptide. To learn more from these findings, the aim of this study is to relate the NMR-based structure of a triazolyl-bridged peptide to its antimicrobial activity against Gram-positive and Gram-negative bacteria in comparison to its linear analogues. As we show, the triazole modification indeed induces a well-defined α-helical structure, resulting in an improved positive electrostatic surface potential on one side of the peptide and clustering of hydrophilic and hydrophobic residues on opposite surface areas of the molecule. Systematic alanine substitution further suggested that the side chains of arginine 3 and 7 and of asparagine 11 have a stronger productive impact on antimicrobial activity than those of lysine 4, 8, and 12. As shown by micelle-bound peptide structures determined by NMR, we identify arginine 3 and asparagine 11 as presumable membrane-interacting residues. Collectively, our NMR-based analysis provides evidence that an α-helical structure enhances antimicrobial activity by creating positively charged and hydrophilic, and hydrophobic areas as molecular surface signatures, potentially promoting the interaction of the peptide with the cellular target membrane. |
| Publikationsart: | Article |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.5c00101 |
| Zugangs-URL: | https://hdl.handle.net/2158/1430395 https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5c00101?ref=article_openPDF https://doi.org/10.1021/acs.biochem.5c00101 |
| Rights: | CC BY NC ND |
| Dokumentencode: | edsair.doi.dedup.....3f5e283778fa56df8c8e48bc85045cc1 |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | The increase in antibacterial resistance is one of the greatest challenges in modern medicine, driving an urgent need to develop new drugs to combat resistant pathogens. Peptides represent a promising class of molecules that can be efficiently designed to exhibit high antimicrobial efficacy. Recently, we have highlighted how prestructuring by a triazolyl-bridge significantly enhances the activity of an antimicrobial peptide. To learn more from these findings, the aim of this study is to relate the NMR-based structure of a triazolyl-bridged peptide to its antimicrobial activity against Gram-positive and Gram-negative bacteria in comparison to its linear analogues. As we show, the triazole modification indeed induces a well-defined α-helical structure, resulting in an improved positive electrostatic surface potential on one side of the peptide and clustering of hydrophilic and hydrophobic residues on opposite surface areas of the molecule. Systematic alanine substitution further suggested that the side chains of arginine 3 and 7 and of asparagine 11 have a stronger productive impact on antimicrobial activity than those of lysine 4, 8, and 12. As shown by micelle-bound peptide structures determined by NMR, we identify arginine 3 and asparagine 11 as presumable membrane-interacting residues. Collectively, our NMR-based analysis provides evidence that an α-helical structure enhances antimicrobial activity by creating positively charged and hydrophilic, and hydrophobic areas as molecular surface signatures, potentially promoting the interaction of the peptide with the cellular target membrane. |
|---|---|
| ISSN: | 15204995 00062960 |
| DOI: | 10.1021/acs.biochem.5c00101 |