We have developed the chemistry to conjugate a pyrroloindole tripeptide (CDPI3) analog of CC-1065 to the 5' or 3' ends of any oligodeoxyribonucleotide (ODN). The resultant conjugates hybridize sequence specifically to complementary DNA and RNA strands, yet do not interact with double-stranded DNA. The conjugated CDPI3 moiety can significantly stabilize short duplexes by binding to the minor groove. In light of these results, we will evaluate the potential of these conjugates as anti sense and antigene agents. The ability of ODN-CDPI3 conjugates to sequence specifically inhibit replication, transcription and translation will be investigated using simple in vitro model systems. Limited cell culture studies will be initiated to evaluate the potential of these modified ODNs for use as anti sense, anti viral or anti-cancer agents.National Institute of General Medical Sciences (NIGMS)
