Mechanism of action of cyclic antimicrobial peptides

• Autores: Anna Díaz Cirac
• Directores de la Tesis: Pedro Salvador Sedano (dir. tes.), Marta Planas Grabuleda (dir. tes.), Lidia Feliu Soley (dir. tes.)
• Lectura: En la Universitat de Girona ( España ) en 2011
• Idioma: inglés
• Tribunal Calificador de la Tesis: María Joao Ramos (presid.), Carles Eduard Curutchet Barat (secret.), Paolo Carloni (voc.), Lorenzo Stella (voc.), Manuel Nuno Melo (voc.)
• Materias:
  • Matemáticas
    • Ciencia de los ordenadores
      • Diseño con ayuda de ordenador
  • Química
    • Bioquímica
      • Péptidos
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • 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.