Thiol-free reducing agents in electrophoretic separations and FASP proteolytic digestions for the analysis of metal-binding proteins

The analysis of the complexes between metal-based chemotherapeutic drugs and proteins in biological samples, such as cisplatin or oxaliplatin, can be a challenge due to metal strong reactivity towards S-donor molecules such as dithiothreitol (DTT) or b-mercaptoethanol (BME), usually employed as redu...

Descripción completa

Detalles Bibliográficos
Autores: Moraleja, I, Moreno Gordaliza, María Estefanía, Mena Fernández, María Luz, Gómez Gómez, María Milagros
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/34099
Acceso en línea:https://hdl.handle.net/20.500.14352/34099
Access Level:acceso abierto
Palabra clave:543
Metal-binding proteins
OFFGEL-IEF
FASP
ICP-MS
Thiol-free reductants
nLC–ESI-LTQ-MS/MS
Química analítica (Química)
2301 Química Analítica
Descripción
Sumario:The analysis of the complexes between metal-based chemotherapeutic drugs and proteins in biological samples, such as cisplatin or oxaliplatin, can be a challenge due to metal strong reactivity towards S-donor molecules such as dithiothreitol (DTT) or b-mercaptoethanol (BME), usually employed as reducing agents in electrophoretic separations and proteolytic digestions for LC–MS/MS analysis. This protocol describes the use of the thiol-free reducing trialkylphosphines, such as tributylphosphine (TBP) and tris(2-carboxyethyl)phosphine (TCEP) as suitable reagents for the preservation of the metal-protein complexes during OFFGEL-IEF and SDS-PAGE separations, respectively. Moreover, the filter-aided sample preparation (FASP) method is presented as an advantageous option to perform tryptic in-solution digestions of metal–protein complexes in combination with OFFGEL-IEF separations.