Designed metallopeptides as tools in Chemical Biology

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...

Descripción completa

Detalles Bibliográficos
Autor: Barka, Ghofrane
Tipo de recurso: tesis doctoral
Fecha de publicación:2017
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/16429
Acceso en línea:http://hdl.handle.net/10347/16429
Access Level:acceso abierto
Palabra clave:Materias::Investigación::23 Química::2302 Bioquímica::230202 Aminoácidos
Materias::Investigación::23 Química::2302 Bioquímica::230206 Quimioterapia
Materias::Investigación::23 Química::2302 Bioquímica::230224 Péptidos
Materias::Investigación::23 Química::2303 Química inorgánica::230307 Compuestos de coordinación
Descripción
Sumario: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.