Tethered naphthalene diimide-based intercalators for DNA triplex stabilization

The synthesis and tripler stabilizing properties of oligodeoxyribonucleotid es functionalized at the 5'-and/or 3'-termini with a naphthalene diimide-ba sed (NDI) intercalator is described. The NDI intercalator was prepared in a single step from the corresponding dianhydride and was attached to the 5'- terminus of an oligodeoxyribonucleotide following a reverse coupling proced ure. The DMT protecting group was removed and the sequence phosphitylated t o generate the phosphoramidite derivative on the 5'-terminus of the support -bound oligodeoxyribonucleotide. The NDI intercalator with a free hydroxyl was then added in the presence of tetrazole, Attachment of the NDI to the 3 '-terminus relied upon a tethered amino group that could be functionalized first with the naphthalene dianhydride, which was subsequently converted to the diimide, Using both procedures, an oligonucleotide conjugate was prepa red having the NDI intercalator at both the 5'- and 3'-termini. Thermal den aturation studies were used to determine the remarkable gain in stability f or triplexes formed when the NDI-conjugated oligonucleotide was present as the third strand in the complex.