SYNTHESIS OF NETROPSIN AND DISTAMYCIN ANALOGS BEARING O-CARBORANE ANDTHEIR DNA RECOGNITION

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