Mechanism of action of cyclic antimicrobial peptides
This PhD thesis is the result of the combination of experimental and computational techniques with the aim of understanding the mechanism of action of de novo cyclic decapeptides with high antimicrobial activity. By experimental techniques the influence of the replacement of the phenylalanine for tr...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/38252 |
| Acceso en línea: | http://hdl.handle.net/10803/38252 http://mediaserver.csuc.cat/tdx/documents/16/04/09/160409284258579343266255546718770547416/ |
| Access Level: | acceso abierto |
| Palabra clave: | Cyclic peptides Pèptids cíclics Péptidos cíclicos Structure-function relationship Relació estructura-funció Relación estructura-función Antimicrobial peptides Pèptids antimicrobials Péptidos antimicrobiales De novo design Molecular dynamics Dinàmica molecular Dinámica molecular Bacterial membrane Membrana bacterial 544 |
| Sumario: | This PhD thesis is the result of the combination of experimental and computational techniques with the aim of understanding the mechanism of action of de novo cyclic decapeptides with high antimicrobial activity. By experimental techniques the influence of the replacement of the phenylalanine for tryptophan residue in their antimicrobial activity was tested and the stability in human serum was also analyzed, in order to evaluate their potential therapeutic application as antitumor agents. On the other hand, the interaction amongst the peptide BPC194 c(KKLKKFKKLQ), the best candidate from the whole library of cyclic peptides, and a model anionic membrane was simulated. The results showed a structure-function relationship derived from the stable conformation of the peptides involved in the membrane permeabilization. As a result, a rational design was performed being BPC490 the peptide with best antimicrobial activity compared with the best active peptide from the original library. |
|---|