SYNTHESIS, HYBRIDIZATION PROPERTIES, NUCLEASE STABILITY, AND CELLULARUPTAKE OF THE OLIGONUCLEOTIDE-AMINO-BETA-CYCLODEXTRINS AND ADAMANTANECONJUGATES

Synthesis of the oligonucleotides conjugated with amino derivatives of beta-cyclodextrin and adamantane, at the 3'-end of host oligonucleoti de, has been described. The oligonucleotide conjugates were examined f or their nuclease stability, hybridization properties, and cellular up take. The oligonucleotide conjugates had increased nuclease resistance compared to their parent oligonucleotides. Conjugation of adamantane to the oligonucleotides did not adversely affect the ability of the ol igonucleotides to hybridize with their complementary RNA. Conjugation with amino derivatives of beta-cyclodextrin, however, significantly de stabilized the duplex formation. In the cellular uptake studies, we fo und that amino derivatives of beta-cyclodextrin attached at 3'-end of the oligonucleotides did not help to increase the uptake by cells. Cel lular uptake of oligonucleotide-adamantane conjugates in association w ith 2-(hydroxypropyl)-beta-cyclodextrin (HPCD) as a ''carrier'' was si gnificantly higher than that of control oligonucleotides.