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Consecutive 5′- and 3′-amide linkages stabilise antisense oligonucleotides and elicit an efficient RNase H response

Consecutive 5′- and 3′-amide linkages stabilise antisense oligonucleotides and elicit an efficient RNase H response
Consecutive 5′- and 3′-amide linkages stabilise antisense oligonucleotides and elicit an efficient RNase H response
Antisense oligonucleotides are now entering the clinic for hard-to-treat diseases. New chemical modifications are urgently required to enhance their drug-like properties. We combine amide coupling with standard oligonucleotide synthesis to assemble backbone chimera gapmers that trigger an efficient RNase H response while improving serum life time and cellular uptake.
1359-7345
5496-5499
Epple, Sven
0a1f70bd-7366-48a9-a1ee-7d747ff652ab
Thorpe, Cameron
2c768b7c-a57a-4f5f-8e64-cae8c9f45aa6
Baker, Ysobel
4fceec1f-89ed-4a32-a753-8967daf6763a
El-Sagheer, Afaf H
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Epple, Sven
0a1f70bd-7366-48a9-a1ee-7d747ff652ab
Thorpe, Cameron
2c768b7c-a57a-4f5f-8e64-cae8c9f45aa6
Baker, Ysobel
4fceec1f-89ed-4a32-a753-8967daf6763a
El-Sagheer, Afaf H
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

Epple, Sven, Thorpe, Cameron, Baker, Ysobel, El-Sagheer, Afaf H and Brown, Tom (2020) Consecutive 5′- and 3′-amide linkages stabilise antisense oligonucleotides and elicit an efficient RNase H response. Chemical Communications, 2020 (41), 5496-5499, [56]. (doi:10.1039/D0CC00444H).

Record type: Article

Abstract

Antisense oligonucleotides are now entering the clinic for hard-to-treat diseases. New chemical modifications are urgently required to enhance their drug-like properties. We combine amide coupling with standard oligonucleotide synthesis to assemble backbone chimera gapmers that trigger an efficient RNase H response while improving serum life time and cellular uptake.

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More information

Accepted/In Press date: 5 March 2020
Published date: 15 April 2020

Identifiers

Local EPrints ID: 473065
URI: http://eprints.soton.ac.uk/id/eprint/473065
ISSN: 1359-7345
PURE UUID: 70b6cc27-ea21-4beb-92a7-a2ae99f04089
ORCID for Ysobel Baker: ORCID iD orcid.org/0000-0002-0266-771X
ORCID for Afaf H El-Sagheer: ORCID iD orcid.org/0000-0001-8706-1292

Catalogue record

Date deposited: 09 Jan 2023 18:54
Last modified: 17 Mar 2024 04:17

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Contributors

Author: Sven Epple
Author: Cameron Thorpe
Author: Ysobel Baker ORCID iD
Author: Afaf H El-Sagheer ORCID iD
Author: Tom Brown

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