Direct and Topoisomerase II Mediated DNA Damage by Bis-3-chloropiperidines: The Importance of Being an Earnest G.

ABSTRACT: Bis-3-chloropiperidines are a new class of DNA-active compounds capable of alkylating nucleobases and inducing strand cleavage. In this study, we investigated the reactivity of these mustard-based agents with both single- and double-stranded DNA constructs. Polyacrylamide gel electrophoresis (PAGE) and electrospray ionization mass spectrometry (ESI-MS) were used to obtain valuable insight into their mechanism at the molecular level and to investigate their time- and concentration-dependent activity. The results revealed the preferential formation of mono- and bifunctional adducts at nucleophilic guanine sites. In a stepwise fashion, alkylation was followed by depurination and subsequent strand scission at the ensuing apurinic site. We demonstrated that the covalent modifications introduced

SUBMITTER: Sosic A 

PROVIDER: S-EPMC7054790 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature