Insights into the effect of the membrane environment on the threedimensional structure-function relationship of antimicrobial peptides
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| Autors: | , , , |
|---|---|
| Format: | actas de congreso |
| Data de publicació: | 2020 |
| Descripció: | Antimicrobial peptides (AMPs) are host defense biomolecules with widespread distribution in all the three life domains: bacteria, archaea and eukaryota. The boom of recent studies in the area of AMPs has been motivated for the hunt of new antibiotics in response to the loss of potency of current ones. Here, we propose to study AMPs in different membrane environments for identification of descriptors defining bioactivity and cytotoxicity. This is accomplished by selecting a set of AMPs whose relevant conformations have been elucidated in membrane mimics using solution and solid state NMR techniques. Then, the physicochemical characterization of the structures are carried out using a novel bioinformatic and lipophilic tool for peptides R-based language called BioLiPeR,which uses lipophilicity descriptors that takes into account both the structural dependence of the conformational preferences of AMPs as well as the influence of pH to provide a consistent description of pH-adapted lipophilicity ofpeptides and proteins. Finally, 3D structure-function relationship studies of AMPs between in vitro biological activities, e.g., minimum inhibition concentration, hemolytic activity and cytotoxicity assays, and the structure-based lipophilic descriptors of the peptides for each membrane-mimetic have shown successful results to determine the bioactivity of AMPs as long as these analyzes are carried out in the same membrane mimetic system, thus indicating a mimic-dependence. Our resultshave the potential to contribute to the stalled search for new antimicrobial agents through the application of state-of-the-art techniques for structural elucidation of peptides and an improved description of lipophilicity in amino acid residues through theoretical formalisms. |
| Pais: | Kérwá |
| Institution: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| Idioma: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/103579 |
| Accés en línia: | https://hdl.handle.net/10669/103579 https://doi.org/10.1016/j.bpj.2019.11.1394 |
| Paraula clau: | antimicrobial peptides membrane environments NMR spectroscopy bioactivity descriptors cytotoxicity BioLiPeR lipophilicity structure–function relationship |