title: Synthesis, hybridization properties, nuclease stability, and cellular uptake of the oligonucleotide--amino-beta-cyclodextrins and adamantane conjugates.
abstract: Synthesis of the oligonucleotides conjugated with amino derivatives of beta-cyclodextrin and adamantane, at the 3'-end of host oligonucleotide, has been described. The oligonucleotide conjugates were examined for their nuclease stability, hybridization properties, and cellular uptake. 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 oligonucleotides to hybridize with their complementary RNA. Conjugation with amino derivatives of beta-cyclodextrin, however, significantly destabilized the duplex formation. In the cellular uptake studies, we found that amino derivatives of beta-cyclodextrin attached at 3'-end of the oligonucleotides did not help to increase the uptake by cells. Cellular uptake of oligonucleotide-adamantane conjugates in association with 2-(hydroxypropyl)-beta-cyclodextrin (HPCD) as a "carrier" was significantly higher than that of control oligonucleotides.
authors.affiliation: Hybridon, Inc., Worcester, Massachusetts 01605, USA.
authors.forename: I
authors.initials: I
authors.lastname: Habus
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000218:Adamantane; D000588:Amines; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D018075:RNA, Complementary / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000588:Amines; D003505:Cyclodextrins; D006001:Glycoconjugates; D007202:Indicators and Reagents; D018075:RNA, Complementary; D014764:Viral Proteins; C069983:gene 43 protein, Enterobacteria phage T4; D004259:DNA-Directed DNA Polymerase; D000218:Adamantane