RESUMEN

A dynamic equilibrium between covalent 1:1 hairpin and 2:1 duplex DNA adducts of a pyrrolobenzodiazepine (PBD) minor groove binding agent () has been observed for the first time. The equilibrium, which establishes over 1 hour and must require unfolding of both types of adducts, is surprising given that PBDs normally require DNA minor groove structure for binding and take 24 hours for complete reaction with duplex DNA. The equilibrium is interesting from an energetics perspective due to the well known DNA stabilizing effect of PBDs. This observation could have significance for the in vitro and in vivo biological activity of PBDs, as DNA hairpin and loop structures are known to be important in cellular processes such as transcription and replication.

Asunto(s)

Benzodiazepinas/farmacología , Aductos de ADN/química , Aductos de ADN/efectos de los fármacos , ADN/química , ADN/efectos de los fármacos , Conformación de Ácido Nucleico/efectos de los fármacos , Pirroles/farmacología , Secuencia de Bases , Benzodiazepinas/química , Sitios de Unión , Cromatografía Líquida de Alta Presión , Pirroles/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción