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Synthesis and properties of oligonucleotides containing LNA-sulfamate and sulfamide backbone linkages

Synthesis and properties of oligonucleotides containing LNA-sulfamate and sulfamide backbone linkages
Synthesis and properties of oligonucleotides containing LNA-sulfamate and sulfamide backbone linkages

Oligonucleotides hold great promise as therapeutic agents but poor bioavailability limits their utility. Hence, new analogues with improved cell uptake are urgently needed. Here, we report the synthesis and physical study of reduced-charge oligonucleotides containing artificial LNA-sulfamate and sulfamide linkages combined with 2′-O-methyl sugars and phosphorothioate backbones. These oligonucleotides have high affinity for RNA and excellent nuclease resistance.

1523-7060
4137-4141
Zengin Kurt, Belma
2ca2cd73-aa3f-4e9b-84ac-59704935f3ff
Dhara, Debashis
6995af8b-1efa-4109-a3e2-64f5b76b52bc
El-Sagheer, Afaf H.
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Zengin Kurt, Belma
2ca2cd73-aa3f-4e9b-84ac-59704935f3ff
Dhara, Debashis
6995af8b-1efa-4109-a3e2-64f5b76b52bc
El-Sagheer, Afaf H.
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

Zengin Kurt, Belma, Dhara, Debashis, El-Sagheer, Afaf H. and Brown, Tom (2024) Synthesis and properties of oligonucleotides containing LNA-sulfamate and sulfamide backbone linkages. Organic Letters, 26 (19), 4137-4141. (doi:10.1021/acs.orglett.4c01232).

Record type: Article

Abstract

Oligonucleotides hold great promise as therapeutic agents but poor bioavailability limits their utility. Hence, new analogues with improved cell uptake are urgently needed. Here, we report the synthesis and physical study of reduced-charge oligonucleotides containing artificial LNA-sulfamate and sulfamide linkages combined with 2′-O-methyl sugars and phosphorothioate backbones. These oligonucleotides have high affinity for RNA and excellent nuclease resistance.

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Accepted/In Press date: 7 May 2024
e-pub ahead of print date: 8 May 2024
Published date: 17 May 2024

Identifiers

Local EPrints ID: 490872
URI: http://eprints.soton.ac.uk/id/eprint/490872
ISSN: 1523-7060
PURE UUID: cd6a300f-8909-49cc-9d55-3578d676e09b
ORCID for Afaf H. El-Sagheer: ORCID iD orcid.org/0000-0001-8706-1292

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Date deposited: 07 Jun 2024 16:40
Last modified: 08 Jun 2024 01:40

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Contributors

Author: Belma Zengin Kurt
Author: Debashis Dhara
Author: Afaf H. El-Sagheer ORCID iD
Author: Tom Brown

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