Amino-acyl tXNA as inhibitors or amino acid donors in peptide synthesis.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
11 11 2022
Historique:
accepted: 21 10 2022
revised: 17 10 2022
received: 21 07 2022
pubmed: 10 11 2022
medline: 16 12 2022
entrez: 9 11 2022
Statut: ppublish

Résumé

Xenobiotic nucleic acids (XNAs) offer tremendous potential for synthetic biology, biotechnology, and molecular medicine but their ability to mimic nucleic acids still needs to be explored. Here, to study the ability of XNA oligonucleotides to mimic tRNA, we synthesized three L-Ala-tXNAs analogs. These molecules were used in a non-ribosomal peptide synthesis involving a bacterial Fem transferase. We compared the ability of this enzyme to use amino-acyl tXNAs containing 1',5'-anhydrohexitol (HNA), 2'-fluoro ribose (2'F-RNA) and 2'-fluoro arabinose. L-Ala-tXNA containing HNA or 2'F-RNA were substrates of the Fem enzyme. The synthesis of peptidyl-XNA and the resolution of their structures in complex with the enzyme show the impact of the XNA on protein binding. For the first time we describe functional tXNA in an in vitro assay. These results invite to test tXNA also as substitute for tRNA in translation.

Identifiants

pubmed: 36350642
pii: 6814473
doi: 10.1093/nar/gkac1023
pmc: PMC9723616
doi:

Substances chimiques

Amino Acids 0
Nucleic Acids 0
Oligonucleotides 0
Peptides 0
RNA, Transfer, Ala 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11415-11425

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Lauriane Rietmeyer (L)

INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, F-75006 Paris, France.

Inès Li De La Sierra-Gallay (I)

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay 91198, Gif-sur-Yvette, France.

Guy Schepers (G)

Laboratory of Medicinal Chemistry, Rega Institute for Biomedical Research, KU Leuven, Herestraat 49, Box 1041, 3000 Leuven, Belgium.

Delphine Dorchêne (D)

INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, F-75006 Paris, France.

Laura Iannazzo (L)

Université Paris Cité, CNRS UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, F-75006Paris, France.

Delphine Patin (D)

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay 91198, Gif-sur-Yvette, France.

Thierry Touzé (T)

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay 91198, Gif-sur-Yvette, France.

Herman van Tilbeurgh (H)

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay 91198, Gif-sur-Yvette, France.

Piet Herdewijn (P)

Laboratory of Medicinal Chemistry, Rega Institute for Biomedical Research, KU Leuven, Herestraat 49, Box 1041, 3000 Leuven, Belgium.

Mélanie Ethève-Quelquejeu (M)

Université Paris Cité, CNRS UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, F-75006Paris, France.

Matthieu Fonvielle (M)

INSERM UMR-S 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, F-75006 Paris, France.

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