DNA-SEQUENCE RECOGNITION BY BIS-LINKED NETROPSIN AND DISTAMYCIN DERIVATIVES

We studied the interaction of cis-diammine Pt(II)-bridged bis-netropsi n, cis-diammine Pt(II)-bridged bis-distamycin and oligomethylene-bridg ed bis-netropsin with synthetic DNA fragments containing pseudosymmetr ical AT-rich nucleotide sequences and compared it with the interaction of the parent compounds netropsin and distamycin A, For fragments con taining multiple blocks of (A/T)(4) and (T/A)(4) separated by zero, on e, two and three GC-base pairs, DNase I footprinting and CD spectrosco py studies reveal that 5'-TTTTAAAA-3' is the strongest affinity bindin g site for cis-diammine Pt(II)-bridged bis-netropsin and bis-distamyci n, They both bind less strongly to a DNA region containing the sequenc e 5'-AAAATTTT-3'. Netropsin, distamycin A and oligomethylene-bridged b is-netropsin exhibit far less sequence discrimination. (C) 1998 Federa tion of European Biochemical Societies.