Microgonotropens and Their Interactions with DNA. 4. Synthesis of the Tripyrrole Peptides Tren-Microgonotropen-a and -b and Characterization of Their Interactions with dsDNA

Exploration of the novel idea to employ a pyrrole nitrogen of a tripyrrole peptide minor groove binding agent to carry catalytic entities to the phosphates and major groove of DNA has been initiated with the synthesis of dien - microgonotropen-a, -b, and -c (5a, 5b, and 5c). Replacing the carboxyl terminal amidine and amino terminal formyl functionalities of distamycin (Dm) by CH 2 N(CH 3 ) 2 and acetyl substituents, respectively, provides 1, which has greater stability in water than does Dm. The synthetic design allows the N-methyl substituent on the central pyrrole of 1 to be replaced by connectors terminating in a dien ligand [-(CH 2 ) 3 N{(CH 2 ) 3 N(CH 3 ) 2 } 2 (5a), -(CH 2 ) 4 N{(CH 2 ) 3 N - (CH 3 ) 2 } 2 (5b), -(CH 2 ) 5 N{(CH 2 ) 3 N(CH 3 ) 2 } 2 (5c)]