DNA sequence recognition in the minor groove by hairpin microgonotropens

Two novel microgonotropens (MGTs) comprised of hairpin N-propylaminepyrrole polyamides linked to a Hoechst 33258 (Ht) analogue (3 and 4) were synthesized on solid phase by adopting an Fmoc technique using a series of HOBt mediated coupling reactions. The dsDNA-binding properties of MGTs 3 and 4 were determined by thermal denaturation experiments. Both MGTs were found to be selective for their nine-bp match dsDNA sequence 9 and were less tolerant of G/C bp substitutions in the binding region than linear progenitor MGT 1. MGT 3 was intolerant of a G/C substitution located in the middle of the binding region and did not bind to sequences 13 and 14. MGT 4 also did not bind to sequence 13, and its linker-bound Ht moiety was found to be more sensitive to a G/C substitution in the Ht-binding target, as demonstrated by the lack of binding to sequence 16.