Tethered naphthalene diimide-based intercalators for DNA triplex stabilization.
The synthesis and triplex stabilizing properties of oligodeoxyribonucleotides functionalized at the 5'- and/or 3'-termini with a naphthalene diimide-based (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 procedure. The DMT protecting group was removed and the sequence phosphitylated to 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 oligonucleo-tide conjugate was prepared having the NDI intercalator at both the 5'- and 3'-termini. Thermal denaturation studies were used to determine the remarkable gain in stability for triplexes formed when the NDI-conjugated oligonucleotide was present as the third strand in the complex.
Gianolio
D A
DA
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA.
Segismundo
J M
JM
McLaughlin
L W
LW
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D009281:Naphthalenes; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010618:Phenanthrolines; D013816:Thermodynamics
D007094:Imides; D007202:Indicators and Reagents; D007364:Intercalating Agents; C409884:N-(2-(2-hydroxyethoxy)ethyl)-N'-(2-(N,N-dimethylamino)ethyl)-1,4,5,8-naphthalenetetracarboxylic diimide; D009281:Naphthalenes; D009838:Oligodeoxyribonucleotides; D010618:Phenanthrolines; C542131:naphthalenediimide; D004247:DNA