Tethered naphthalene diimide intercalators enhance DNA triplex stability

Naphthalene diimides function as effective intercalators and when tethered to the 5 ' -terminus of a pyrimidine-rich oligonucleotide can contribute si gnificantly to the overall stabilization of DNA triplexes. This stabilizati on can be further enhanced by alterations to the linker tethering the DNA s equence and the intercalator. Less flexible linkers, and particularly one w ith a phenyl ring present, appear to permit the stabilization afforded by t he bound intercalator to be transferred more effectively to the three-stran ded complex. The conjugate containing the phenyl linker exhibits a TM value that is increased by 28 degreesC relative to the unconjugated triplex. Tha t the linker itself contributes to the observed stabilization is clear sinc e introduction of the phenyl linker increases the observed Tm by 11 degrees C relative to a simple flexible linker. (C) 2001 Elsevier Science Ltd. All rights reserved.