Synthesis of structurally diverse major groove DNA interstrand crosslinks using three different aldehyde precursors.

ABSTRACT: DNA interstrand crosslinks (ICLs) are extremely cytotoxic lesions that block essential cellular processes, such as replication and transcription. Crosslinking agents are widely used in cancer chemotherapy and form an array of structurally diverse ICLs. Despite the clinical success of these agents, resistance of tumors to crosslinking agents, for example, through repair of these lesions by the cellular machinery remains a problem. We have previously reported the synthesis of site-specific ICLs mimicking those formed by nitrogen mustards to facilitate the studies of cellular responses to ICL formation. Here we extend these efforts and report the synthesis of structurally diverse major groove ICLs that induce severe, little or no distortion in the DNA. Our approach employs the incorporation o

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC4066762 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature