Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences , Tokyo University of Science , 2641 Yamazaki , Noda , Chiba 278-8510 , Japan.
Department of Medical Genome Sciences, Graduate School of Frontier Sciences , The University of Tokyo , Bioscience Building 702, 5-1-5 Kashiwanoha , Kashiwa , Chiba 277-8562 , Japan.
J Org Chem. 2019 Dec 6;84(23):15032-15041. doi: 10.1021/acs.joc.9b01257. Epub 2019 Nov 13.
Boranophosphate (PB) DNAs are promising antisense oligonucleotide candidates because of their attractive features, such as high nuclease resistance and low toxicity. However, a full boranophosphate backbone modification to antisense DNAs causes reduced duplex formation with complementary RNAs and reduced antisense activity. In this study, an efficient solid-phase synthesis of phosphate/boranophosphate (PO/PB) chimeric DNA was achieved by the combination of the -phosphonate and -boranophosphonate methods. The physiological and biological properties of the synthesized PO/PB chimeric DNAs were also evaluated. The strategy employed herein can facilitate the design and synthesis of PO/PB chimeric DNAs containing site-specific boranophosphate modifications.
硼酸盐 DNA（PB DNA）是很有前途的反义寡核苷酸候选物，因为它们具有吸引人的特性，如高核酸酶抗性和低毒性。然而，将反义 DNA 的全硼酸盐骨架修饰会导致与互补 RNA 的双链体形成减少和反义活性降低。在这项研究中，通过 -磷酸酯和 -硼磷酰酯方法的结合，实现了磷酸酯/硼酸盐（PO/PB）嵌合 DNA 的高效固相合成。还评估了合成的 PO/PB 嵌合 DNA 的生理和生物学特性。本文所采用的策略可以促进含有特定硼酸盐修饰的 PO/PB 嵌合 DNA 的设计和合成。
