Effects of pendant groups at phosphorus on binding properties of d-ApA analogues.
The interaction of several synthetic analogues of d-ApA with Poly U and Poly dT was examined to explore the effects of substituents at phosphorus on binding properties of oligonucleotides. These analogues contained a bulky, lipophilic group (2,2,2-trichloroethoxy or 2,2,2-trichloro-1,1-dimethylethoxy) a small, uncharged hydrogen-bonding group (amido), or a cationic phosphoramidate (2-aminoethylamido, protonated in neutral aqueous media) in place of the anionic oxygen of the internucleotide phosphate. As determined by "melting curves" each formed a complex with Poly U more stable than the Poly U.d-ApA complex. Binding to Poly dT was comparable or in some cases stronger. Checks on composition (mixing curves) revealed the expected stoichiometry of ldA:2U (or 2dT). Stereochemistry at phosphorus influenced stability of the complexes, but the effect was not a major one. These results suggest that oligonucleotides containing large, lipophilic groups, as well as small non-ionic groups (e.g., the methyl phosphonates) or polar groups, could be useful as probes in hybridization experiments.
R L
RL
Letsinger
S A
SA
Bach
J S
JS
Eadie
D003838:Deoxyadenine Nucleotides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007700:Kinetics; D011072:Poly U; D013329:Structure-Activity Relationship
D003838:Deoxyadenine Nucleotides; D007202:Indicators and Reagents; D011072:Poly U