Synthesis of Netropsin and Distamycin Analogues Bearing o-Carborane and Their DNA Recognition

Netropsin and distamycin A analogues containing o-carborane framework, 4a-c and 5a-c, respectively, were synthesized to investigate DNA binding sequence of these molecules. Cascade type polyols were attached to the carboranes in certain cases; 4b and 5b had the diol unit and 4c and 5c possessed the tetraol unit, whereas 4a and 5a had no hydroxy group. MPE-Fe(II) footprinting on the 216 base pair Pvu I/ Bam HI restriction fragment from pBLUESCRIPT KS(+1-) (bp 2958) indicated that 4a and 5a bound only slightly to the DNA fragment, whereas 4b and 5b bearing two hydroxy groups bound to the A,T-rich base pairs. The compounds containing four hydroxy groups 4c and 5c bound most selectively to the DNA fragments. In general, the compounds 5 containing three pyrrole rings in their molecules bound to the DNA more selectively than the corresponding two pyrrole ring-bearing compounds 4.