Habus I, Zhao Q, Agrawal S
Hybridon, Inc., Worcester, Massachusetts 01605, USA.
Bioconjug Chem. 1995 Jul-Aug;6(4):327-31. doi: 10.1021/bc00034a001.
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.
已报道了在主体寡核苷酸的3'端合成与β-环糊精和金刚烷的氨基衍生物共轭的寡核苷酸。对寡核苷酸缀合物的核酸酶稳定性、杂交特性和细胞摄取进行了检测。与它们的亲本寡核苷酸相比，寡核苷酸缀合物具有更高的核酸酶抗性。金刚烷与寡核苷酸的共轭不会对寡核苷酸与其互补RNA杂交的能力产生不利影响。然而，与β-环糊精的氨基衍生物共轭会显著破坏双链体的形成。在细胞摄取研究中，我们发现连接在寡核苷酸3'端的β-环糊精氨基衍生物无助于增加细胞摄取。作为“载体”的2-(羟丙基)-β-环糊精(HPCD)与寡核苷酸-金刚烷缀合物的细胞摄取显著高于对照寡核苷酸。
