Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages
Joint Authors
Potenza, Nicoletta
Cosconati, Sandro
Mercurio, M. Emilia
Novellino, Ettore
Russo, Aniello
Messere, Anna
Gaglione, Maria
Mosca, Nicola
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-03-26
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
The active components of the RNAi are 21 nucleotides long dsRNAs containing a 2 nucleotide overhang at the 3′ end, carrying 5′-phosphate and 3′-hydroxyl groups (siRNAs).
Structural analysis revealed that the siRNA is functionally bound at both ends to RISC.
Terminal modifications are considered with interest as the introduction of chemical moieties interferes with the 3′ overhang recognition by the PAZ domain and the 5′-phosphate recognition by the MID and PIWI domains of RISC.
Herein, we report the synthesis of modified siRNAs containing terminal amide linkages by introducing hydroxyethylglycine PNA (hegPNA) moieties at 5′, and at 3′ positions and on both terminals.
Results of gene silencing studies highlight that some of these modifications are compatible with the RNAi machinery and markedly increase the resistance to serum-derived nucleases even after 24 h of incubation.
Molecular docking simulations were attained to give at atomistic level a clearer picture of the effect of the most performing modifications on the interactions with the human Argonaute 2 PAZ, MID, and PIWI domains.
This study adds another piece to the puzzle of the heterogeneous chemical modifications that can be attained to enhance the silencing efficiency of siRNAs.
American Psychological Association (APA)
Gaglione, Maria& Mercurio, M. Emilia& Potenza, Nicoletta& Mosca, Nicola& Russo, Aniello& Novellino, Ettore…[et al.]. 2014. Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages. BioMed Research International،Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-506562
Modern Language Association (MLA)
Gaglione, Maria…[et al.]. Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages. BioMed Research International No. 2014 (2014), pp.1-15.
https://search.emarefa.net/detail/BIM-506562
American Medical Association (AMA)
Gaglione, Maria& Mercurio, M. Emilia& Potenza, Nicoletta& Mosca, Nicola& Russo, Aniello& Novellino, Ettore…[et al.]. Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-506562
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-506562