OLIGOTHYMIDYLATES WITH ALTERNATING (3'-3') AND (5'-5') PHOSPHODIESTER LINKAGES

私家侦探设计了具有交替的（3'至3'）-和 （5'至5'）-核苷酸间磷酸二酯键， 这些寡核苷酸可能不会被核酸酶快速识别， 天然低聚物。 一个阿尔法的替代品- 在（3'至（4'）核苷酸序列中，β-单脱氧核糖核苷酸是β-单脱氧核糖核苷酸。 3 '）-和（5'到5 '）-核苷酸间键合基序，以提高 寡核苷酸类似物的杂交性质。 博士古贺合成了所需的α-脱氧核糖核苷 亚磷酰胺和α，β-寡聚胸苷酸类似物， 与其它寡核苷酸类似物（硫代磷酸酯）一起沿着制备 和α-寡聚胸苷酸）和互补的β- 寡脱氧核糖腺苷酸以进行有意义的对照实验。 交替的α，β-寡聚胸苷酸与交替的（3'至3'）-和 （5'至5'）-核苷酸间磷酸二酯键与它们的 互补的β-寡脱氧核糖腺苷酸， 硫代磷酸酯低聚物。 α，β-寡聚胸苷酸代表一种 有趣的一类寡核苷酸类似物在磷上是非手性的。 博士古贺目前正在合成四种不同的阿尔法- 脱氧核糖核苷亚磷酰胺在试图制备α， β-寡核苷酸，其与由以下的rev基因编码的mRNA互补： HIV-1 寡核苷酸类似物的抗HIV活性将是 在慢性感染的H9细胞中进行了测试， NCI的Mitsuya 在α，β- 寡聚胸苷酸和聚dA-poly dT双链体也将通过 聚丙烯酰胺凝胶电泳迁移率变化实验。

The P.I. has designed oligothymidylates having alternating (3' to 3')- and (5' to 5')-internucleotidic phosphodiester linkages based on the assumption that these oligonucleotides may not be recognized as rapidly by nucleases as natural oligomers. The alternate substitution of an alpha- monodeoxyribonucleotide for a beta-monodeoxyribonucleotide in the (3' to 3')- and (5' to 5')-internucleotidic linkage motif was achieved to improve the hybridizing properties of the oligonucleotide analogues. Dr. Koga synthesized the required alpha-deoxyribonucleoside phosphoramidites and the alpha, beta-oligothymidylate analogues were prepared along with the other oligonucleotide analogues (phosphorothioates and alpha-oligothymidylates) and a complementary beta- oligodeoxyriboadenylate to instigate meaningful control experiments. Alternating alpha,beta-oligothymidylates with alternating (3' to 3')- and (5' to 5')-internucleotidic phosphodiester linkages hybridized to their complementary beta-oligodeoxyriboadenylate as tightly as the phosphorothioate oligomer. The alpha,beta-oligothymidylates represent an interesting class of oligonucleotide analogues achiral at phosphorus. Dr. Koga is currently synthesizing the four different alpha- deoxyribonucleoside phosphoramidites in an attempt to prepare an alpha, beta-oligonucleotide complementary to the mRNA encoded by the rev gene of HIV-1. The anti-HIV activity of the oligonucleotide analogue will be tested in chronically infected H9 cells in a collaborative effort with Dr. Mitsuya of NCI. The potential formation of a triple helix between an alpha,beta- oligothymidylate and a poly dA-poly dT duplex will also be investigated by electrophoretic mobility shift experiments on polyacrylamide gels.