Groove- and sequence-selective alkylation of DNA by sulfonate esters tethered to lexitropsins

A series of sulfonate esters that are attached to a noncationic minor-groove-binding N-methylpyrrole dipeptide (Lex) related to netropsin have been synthesized. The compounds prepared differ in two respects: (1) the length [(CH 2 ) 2 vs (CH 2 ) 8 ] of the tether between the DNA affinity binding portion of the molecule and the sulfonate ester and (2) whether a methyl group [MeOSO 2 (CH 2 ) n -Lex] or the dipeptide including the aliphatic tether [MeSO 2 O(CH 2 ) n -Lex] is covalently transferred to the DNA