DNA alkylation promoted by an electron-rich quinone methide intermediate

Abstract

Biological application of conjugates derived from oligonucleotides and quinone methides have previously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substituent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5'-aminohexyloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.

Graphical abstract

Keywords

quione methide / DNA alkylation / reversible covalent reaction / bioconjugation / target-directed modification of nucleic acids

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