Tailored hydrophobic cavities in oligonucleotide-steroid conjugates.
Hydrophobic pockets can be generated readily in aqueous solution by hybridization of oligonucleotide conjugates containing one or two androstane units inserted into each strand by short phosphoryl linkers. Both double- and triple-stranded complexes formed by the conjugates are stabilized by adding to the solution a water-soluble hydrophobic substrate, 3,17-diaminoandrostane dihydrochloride, that can bind in the pocket. This substrate has no effect on the dissociation of unmodified oligonucleotides, and 1,10-diaminodecane dihydrochloride has no effect on dissociation of complexes of these steroid conjugates under the same conditions. This system provides a new means for selectively modulating and triggering hybridization of oligonucleotide conjugates. Cetyltrimethylammonium bromide strongly enhances the stability of complexes of the steroid conjugates; however, it also leads to precipitation of complexes of unmodified oligonucleotides.
Letsinger
R L
RL
Department of Chemistry and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. r-letsinger@chem.nwu.edu
Chaturvedi
S
S
D000731:Androstanes / Q000737:chemistry; D003959:Diamines / Q000737:chemistry; D007202:Indicators and Reagents; D008968:Molecular Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry*; D013696:Temperature
C065351:1,10-diaminodecane; D000731:Androstanes; D003959:Diamines; D007202:Indicators and Reagents; D009841:Oligonucleotides; D013256:Steroids