Issue 18, 2022, Issue in Progress

Synthesis, gene silencing activity, thermal stability, and serum stability of siRNA containing four (S)-5′-C-aminopropyl-2′-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine)

Abstract

Herein, we report the synthesis of (S)-5′-C-aminopropyl-2′-O-methyladenosine and (S)-5′-C-aminopropyl-2′-O-methylguanosine phosphoramidites and the properties of small interfering RNAs (siRNAs) containing four (S)-5′-C-aminopropyl-2′-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine). The siRNAs containing (S)-5′-C-aminopropyl-nucleosides at the 3′- and 5′-regions of the passenger strand were well tolerated for RNA interference (RNAi) activity. Conversely, the (S)-5′-C-aminopropyl modification in the central region of the passenger strand decreased the RNAi activity. Furthermore, the siRNAs containing three or four consecutive (S)-5′-C-aminopropyl-2′-O-methylnucleosides at the 3′- and 5′-regions of the passenger strand exhibited RNAi activity similar to that of the corresponding 2′-O-methyl-modified siRNAs. Finally, it was observed that (S)-5′-C-aminopropyl modifications effectively improved the serum stability of the siRNAs, compared with 2′-O-methyl modifications. Therefore, (S)-5′-C-aminopropyl-2′-O-methylnucleosides would be useful for improving the serum stability of therapeutic siRNA molecules without affecting their RNAi activities.

Graphical abstract: Synthesis, gene silencing activity, thermal stability, and serum stability of siRNA containing four (S)-5′-C-aminopropyl-2′-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine)

Supplementary files

Article information

Article type
Paper
Submitted
02 Feb 2022
Accepted
30 Mar 2022
First published
12 Apr 2022
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2022,12, 11454-11476

Synthesis, gene silencing activity, thermal stability, and serum stability of siRNA containing four (S)-5′-C-aminopropyl-2′-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine)

R. Kajino, S. Sakamoto and Y. Ueno, RSC Adv., 2022, 12, 11454 DOI: 10.1039/D2RA00705C

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