Designed metallopeptides as tools in chemical biology

  1. Barka , Ghofrane
Supervised by:
  1. Marco Eugenio Vázquez Sentís Director
  2. Miguel Vázquez López Co-director

Defence university: Universidade de Santiago de Compostela

Fecha de defensa: 15 December 2017

Committee:
  1. Ignacio Alfonso Rodríguez Chair
  2. Elena Pazos Secretary
  3. Fernando José López García Committee member
Department:
  1. Department of Organic chemistry

Type: Thesis

Abstract

A series of Ru(II) metallopeptides featuring the dipyrido[3,2-a:2',3'-c]phenazine ligand (dppz) have been synthesized through solid-phase peptide synthesis (SPPS) methods. Spectroscopic studies indicate that functionalization with an oligoarginine basic tail causes a drastic change in the binding mode and a great increase of the affinity of these metallopeptides for well-matched B-DNA oligonucleotides over mismacthed DNAs. In addition, the spectroscopic data suggest that both the oligoarginine functionalization and the nature of the ancillary ligands do not cause an increase of the selectivity of these metallopeptides for a particular type of mismatched DNA oligonucleotide. Finally, fluorescence microscopy studies indicate that the oligoarginine functionalization causes the efficient internalization of the metallopeptides into Vero cells, causing apoptotic cell death after a few hours.