Synthesis and characterization of an O(6)-2'-deoxyguanosine-alkyl-O(6)-2'-deoxyguanosine interstrand cross-link in a 5'-GNC motif and repair by human O(6)-alkylguanine-DNA alkyltransferase.

ABSTRACT: O(6)-2'-Deoxyguanosine-alkyl-O(6)-2'-deoxyguanosine interstrand DNA cross-links (ICLs) with a four and seven methylene linkage in a 5'-GNC- motif have been synthesized and their repair by human O6-alkylguanine-DNA alkyltransferase (hAGT) investigated. Duplexes containing 11 base-pairs with the ICLs in the center were assembled by automated DNA solid-phase synthesis using a cross-linked 2'-deoxyguanosine dimer phosphoramidite, prepared via a seven step synthesis which employed the Mitsunobu reaction to introduce the alkyl lesion at the O(6) atom of guanine. Introduction of the four and seven carbon ICLs resulted in no change in duplex stability based on UV thermal denaturation experiments compared to a non-cross-linked control. Circular dichroism spectra of these ICL duplexes exhibited feat

SUBMITTER: McManus FP 

PROVIDER: S-EPMC3021135 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature