Efficient DNA alkylation by a pyrrole-imidazole CBI conjugate with an indole linker: Sequence-specific alkylation with nine-base-pair recognition

Conjugates 7, 8, and 10 of N- methylpyrrole ( Py)- N- methylimidazole ( Im) polyamides and 1,2,9,9a- tetrahydrocyclopropa[ 1,2- c] benz[ 1,2- e] indol- 4- one ( CBI) with a 5- amino- 1H- indole- 2- carbonyl linker were synthesized by Fmoc solid- phase synthesis and a subsequent liquid- phase coupling procedure. The DNA alkylating abilities of conjugates 7, 8, 6b, and 10 were examined using Texas Red- labeled PCR fragments and high- resolution denaturing gel electrophoresis. CBI conjugates 7 and 8 exhibited highly efficient sequence- specific DNA alkylation comparable with previous CBI conjugates with a vinyl linker. In particular, conjugate 10, with a 10- ringed hairpin Py- Im polyamide, alkylated at the adenine of 5 - ACAAATCCA- 3. Introduction of an indole linker greatly facilitated the synthesis of sequence- specific alkylating Py- Im polyamides.