DNA crosslinking, sister chromatid exchange and cytotoxicity of N-2-chloroethylnitrosoureas tethered to minor groove binding peptides

Choroethylnitrosoureas (CENU) are clinically important chemotherapeutic agents whose mechanism of action involves the formation of interstrand DNA crosslinks via an ethane bridge between N1-G and N3-C. CENU generally alkylate G at the N7- and O 6 -positions, with the latter lesion being the precursor to the interstrand crosslink. In previous studies, we reported the synthesis of CENU appended by a C 2 H 4 linker to the N-terminus of DNA minor groove binding dipeptides (lex, information reading peptides) based on N-methylpyrrole-carboxamide subunits. Because of the dipeptide structure, these CENU-lex's react with DNA at adenines associated with lex equilibrium binding sites. No other CENU has been reported to yield A adducts