ALTERNATING ALPHA,BETA-OLIGOTHYMIDYLATES AS MODEL ANTISENSE MOLECULES

交替α,β-寡核苷酸作为模型反义分子

• 批准号: 3792434
• 负责人: S L BEAUCAGE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792434
• 关键词: amides; antisense nucleic acid; conformation; deoxyribonucleosides; deoxyribonucleotides; gel electrophoresis; human immunodeficiency virus 1; messenger RNA; nucleic acid chemical synthesis; nucleotide analog; oligonucleotides; thiophosphate

Alternating alpha,beta-oligothymidylates with alternating (3'-3')- and (5'-5')-internucleotidic phosphodiester linkages have been synthesized to evaluate the stability of these oligonucleotide analogues to nucleases and their hybridization abilities. It was found that these oligomers hybridized to their complementary beta-oligodeoxyriboadenylate as tightly as phosphorothioate oligomers. The alpha,beta- oligothymidylates were also more resistant to the nucleolytic activity of S1 nuclease than that of the phosphorothioate and beta- oligothymidylates. During the last months of his tenure in our laboratory Dr. Koga has synthesized 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 preparation of alpha-deoxyguanosine and its phosphoramidite has been particularly difficult. Since the departure of Dr. Koga in January 1992, this project has not progressed. A replacement for Dr. Koga has not, as yet, been approved. More data are required to complete the study of this interesting class of oligonucleotides achiral at phosphorus. Specifically, it would be worth gathering various physico- chemical properties (thermal denaturation and CD analysis) and extended nucleolytic resistance data before applying these oligonucleotide analogues to antisense experiments.

交替的α，β-寡聚胸苷酸与交替的（3 '-3'）-和 已经合成了（5 '-5'）-核苷酸间磷酸二酯键 为了评价这些寡核苷酸类似物的稳定性， 核酸酶及其杂交能力。 发现这些 与其互补的β-寡脱氧核糖腺苷酸杂交的寡聚物 与硫代磷酸酯低聚物一样紧密。 阿尔法贝塔- 寡胸苷酸对溶核活性的抗性也更强 S1核酸酶比硫代磷酸和β- 寡胸苷酸。 古贺博士在我们实验室任职的最后几个月里， 合成了四种不同的α-脱氧核苷 亚磷酰胺以试图制备α，β-寡核苷酸 与HIV-1的rev基因编码的mRNA互补。 的 α-脱氧鸟苷及其亚磷酰胺的制备， 特别困难。 自从古贺博士一月份离开后 1992年，这个项目没有进展。 接替古贺博士的人 目前尚未得到批准。 需要更多数据才能完成 研究这类有趣的非手性寡核苷酸， 磷 具体来说，这将是值得收集各种物理- 化学性质（热变性和CD分析）和扩展 在应用这些寡核苷酸之前的溶核抗性数据 类似于反义实验。