Derivatization of Mirror-Image l-Nucleic Acids with 2'-OMe Modification for Thermal and Structural Stabilization.

Autor: Dantsu Y; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.; Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, IN, 46202, USA., Zhang W; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.; Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, IN, 46202, USA.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2023 Jun 15; Vol. 24 (12), pp. e202200764. Date of Electronic Publication: 2023 May 16.
DOI: 10.1002/cbic.202200764
Abstrakt: To further expand the functionality and enhance the stability of mirror-image nucleic acids as advanced agents for basic research and therapeutic design, we have synthesized 2'-deoxy-2'-methoxy-l-uridine phosphoramidite and incorporated it into l-DNA and l-RNA by solid-phase synthesis quantitatively. We found that the thermostability of l-nucleic acids is dramatically improved after introducing the modifications. Moreover, we successfully crystallized both l-DNA and l-RNA duplexes containing the 2'-OMe modifications and sharing identical sequences. Crystal structure determination and analysis revealed the overall structures of the mirror-image nucleic acids, and for the first time it was possible to interpret the structural deviations caused by 2'-OMe and 2'-OH groups in the oligonucleotides, which are very similar. This novel chemical nucleic acid modification has the potential to be used to design nucleic acid-based therapeutics and materials in the future.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: