RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000131.xml
PDF herunterladen
Synfacts 2023; 19(01): 0087
DOI: 10.1055/s-0042-1752379
DOI: 10.1055/s-0042-1752379
Innovative Drug Discovery and Development
Novel Dioxane- and Morpholino Nucleotide Analogues with Improved Off-Target Profiles in siRNAs
Authors
Hofmeister A.
*
et al.
Sanofi, Frankfurt am Main, Germany
Small Interfering RNAs Containing Dioxane- and Morpholino-Derived Nucleotide Analogues Show Improved Off-Target Profiles and Chirality-Dependent In Vivo Knock-Down.
J. Med. Chem. 2022;
65: 13736-13752
DOI: 10.1021/acs.jmedchem.2c00873
Small Interfering RNAs Containing Dioxane- and Morpholino-Derived Nucleotide Analogues Show Improved Off-Target Profiles and Chirality-Dependent In Vivo Knock-Down.
J. Med. Chem. 2022;
65: 13736-13752
DOI: 10.1021/acs.jmedchem.2c00873
Significance
The authors describe the synthesis of novel dioxane- and morpholine-based nucleotide precursors. These nucleotides were incorporated at position 7 of an antisense strand leading to improved in vitro off-target profiles due to destabilization of the seed region.
Scroll to top
Comment
Interestingly, the corresponding (2S, 2R) isomers of 1 and 2 also led to improved off-target profiles. However, significantly lower in vivo potencies were observed, potentially due to the inability of these nucleosides to undergo Watson–Crick base paring.
Scroll to top
Scroll to top
Publikationsverlauf
Artikel online veröffentlicht:
16. Dezember 2022
© 2022. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany