Krishna Jayaraman

Synthesis of Cholesteryl Supports and Phosphoramidite for Automated DNA Synthesis of Triple-Helix Forming Oligonucleotides (Tfos)

Abstract DMT-Cholesteryl succinylamino solid supports (CPG, loading: 33 μmole/gram and TentaGel loading: 152 μmole/gram) and DMT-cholesteryl phosphoramidite were prepared for use in automated DNA synthesis of cholesteryl modified TFOs in the synthesis scales from 0.2 to 300 μmole. The modified TFOs were found to have a 5 to 50 fold increase in their uptake properties.

Approaches to Enhance the Binding Affinity and Nuclease Stability of Triplex Forming Oligonucleotides

Abstract The ability of simple azole nucleosides to promote antiparallel triplex formation at non-homopurine duplex targets was explored. It was also shown that spermidine-cholesterol conjugation is effective in enhancing cellular uptake and stability of oligonucleotides.

Synthesis of Triple Helix Forming Oligonucleotides with a Stretched Phosphodiester Backbone

Abstract Total synthesis of novel DMT-phosphoramidites of thymidine (11 and 15) and 2′-deoxyguanosine (8 and 20) have been accomplished. The utility of these modified building blocks in the preparation of triple helix forming oligodeoxyribonucleotides with a stretched phosphodiester backbone has been evaluated. It was found that the oligonucleotides with extended backbones were unable to enhance the binding to duplex targets containing CG or TA base pairs.