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Understanding the transport mechanism of bbb peptide shuttles: thrre and miniap-4 as case studies

  • Autores: Cristina Fuster Juncà
  • Directores de la Tesis: Meritxell Teixidó Turá (dir. tes.), Macarena Sánchez Navarro (dir. tes.), Ernest Giralt Lledó (tut. tes.)
  • Lectura: En la Universitat de Barcelona ( España ) en 2019
  • Idioma: español
  • Tribunal Calificador de la Tesis: Ernesto Nicolás Galindo (presid.), Miriam Royo Expósito (secret.), Paula Alexandra de Carvalho Gomes (voc.)
  • Programa de doctorado: Programa de Doctorado en Química Orgánica por la Universidad de Barcelona
  • Materias:
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  • Resumen
    • The blood-brain barrier is a highly selective permeable barrier that difficult the delivery of potential therapeutics to the brain, however, some peptides have been described to have a capacity to transport different In this thesis we have studied in detail the mechanism of internalization of two described blood-brain barrier peptide shuttles: THRre and MiniAp-4. These two peptides have proved their ability to transport a wide variety of cargoes in vitro and in vivo.

      In the first part of the thesis, we have validated the interaction between THRre and the transferrin receptor using saturated transfer difference (STD) NMR, however it was not possible to obtain a constant of dissociation value with ITC or SAW due to a low affinity between them.

      In the second part, we have studied if differences in the cis/trans proline ratio lead to differences in transport capacity. To this end, several analogues were designed and synthesized. Although no significant differences were observed between analogues, one showed a higher transport capacity for a small cargo as carboxifluorescein. Finally, we aimed to understand the transport mechanism of this peptide by confocal microscopy and photocrosslinking. Results suggest that MiniAp-4 uses a clathrin-dependent and a caveolin pathway mechanism, however, further experiments needs to be done in order to confirm it.


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