English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Synthesis, gene silencing, and molecular modeling studies of 4 '-C-aminomethyl-2 '-O-methyl modified small interfering RNAs.

Gore, K. R., Nawale, G. N., Harikrishna, S., Chittoor, V. G., Pandey, S. K., Höbartner, C., et al. (2012). Synthesis, gene silencing, and molecular modeling studies of 4 '-C-aminomethyl-2 '-O-methyl modified small interfering RNAs. Journal of Organic Chemistry, 77(7), 3233-3245. doi:10.1021/jo202666m.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-88AE-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-C686-C
Genre: Journal Article

Files

show Files
hide Files
:
1464983.pdf (Publisher version), 563KB
 
File Permalink:
-
Name:
1464983.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Göttingen; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1464983_si_001.pdf (Supplementary material), 6MB
Name:
1464983_si_001.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Gore, K. R., Author
Nawale, G. N., Author
Harikrishna, S., Author
Chittoor, V. G., Author
Pandey, S. K., Author
Höbartner, C.1, Author              
Patankar, S., Author
Pradeepkumar, P. I., Author
Affiliations:
1Research Group of Nucleic Acid Chemistry, MPI for biophysical chemistry, Max Planck Society, ou_578605              

Content

show
hide
Free keywords: -
 Abstract: The linear syntheses of 4′-C-aminomethyl-2′-O-methyl uridine and cytidine nucleoside phosphoramidites were achieved using glucose as the starting material. The modified RNA building blocks were incorporated into small interfering RNAs (siRNAs) by employing solid phase RNA synthesis. Thermal melting studies showed that the modified siRNA duplexes exhibited slightly lower Tm (1 °C/modification) compared to the unmodified duplex. Molecular dynamics simulations revealed that the 4′-C-aminomethyl-2′-O-methyl modified nucleotides adopt South-type conformation in a siRNA duplex, thereby altering the stacking and hydrogen-bonding interactions. These modified siRNAs were also evaluated for their gene silencing efficiency in HeLa cells using a luciferase-based reporter assay. The results indicate that the modifications are well tolerated in various positions of the passenger strand and at the 3′ end of the guide strand but are less tolerated in the seed region of the guide strand. The modified siRNAs exhibited prolonged stability in human serum compared to unmodified siRNA. This work has implications for the use of 4′-C-aminomethyl-2′-O-methyl modified nucleotides to overcome some of the challenges associated with the therapeutic utilities of siRNAs.

Details

show
hide
Language(s): eng - English
 Dates: 2012-02-282012-04-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/jo202666m
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Organic Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 77 (7) Sequence Number: - Start / End Page: 3233 - 3245 Identifier: -