A number of oligonucleotide analogues containing internucleoside phosphorothioate linkages and a covalently attached cholesteryl residue was synthesized and tested for activity against HIV-1 in cultures of Molt3 cells. Structural features important for high antiviral activity are the presence of a cholesteryl moiety, a run of terminal phosphorothioate groups, and the presence of nucleoside residues. An increase in length of the tether between cholesteryl and phosphorus from six to 14 atoms has no significant effect on antiviral activity, and up to one-half of the internucleoside links in a cholesteryl-conjugated phosphorothioate oligomer and one-third of the internucleoside links in a nonconjugated phosphorothioate can be replaced with phosphodiester links without much change in antiviral activity. However, replacement of nucleoside units in the oligomers by a simple analogue (-OCH2CH2CH2O-) yields inactive or very weakly active compounds, even in the presence of a cholesteryl group. Dose-response patterns for assays in which cholesteryl-conjugated oligomers are added to test cells either simultaneously or subsequently to viral infection are similar for homooligomer derivatives and for oligomers containing "antisense" sequences, suggesting a similarity in mode of action for the two classes of oligomers in this system.

Antiviral Agents↗

PubMedDate not supplied

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.

Androstanes↗

PubMedDate not supplied

Use of a steroid cyclic disulfide anchor in constructing gold nanoparticle-oligonucleotide conjugates.

A new anchoring group is described for binding oligonucleotides to gold surfaces. On the basis of a ketal derived from 4,5-dihydroxy-1, 2 dithiane and epiandrosterone, it is easy to prepare and to link to oligonucleotides. Gold nanoparticle-oligonucleotide conjugates made using this cyclic disulfide linker serve as effective probes for detecting specific oligonucleotide sequences, and they exhibit much greater stability toward dithiothreitol than corresponding conjugates prepared with the conventional mercaptohexyl group or an acyclic disulfide unit. The high stability toward thiol deactivation likely results, in part at least, from anchoring each oligonucleotide to gold through two sulfur atoms.

DNA Probes↗

PubMedDate not supplied

Stabilization of deoxyadenosine/polynucleotide complexes by 3',5'-di-O-benzoyl substituents.

3',5'-Di-O-benzoyldeoxyadenosine forms stable dT:dA:dT type complexes with poly(dT) and an oligo(dT)-cholesteryl conjugate in dilute aqueous solution. The benzoyl groups play an essential role in stabilizing these "triple stranded" complexes.

Adenosine↗