CEBA: A new heterobifunctional reagent for plasmid DNA functionalization by click chemistry.

Chloroethyl Click chemistry DNA conjugation DNA labelling Heterobifunctional crosslinking reagent p-((2-chloroethyl) ethylamino) benzaldehyde

Journal

International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127

Informations de publication

Date de publication:
15 May 2021
Historique:
received: 19 12 2020
revised: 24 03 2021
accepted: 29 03 2021
pubmed: 5 4 2021
medline: 22 6 2021
entrez: 4 4 2021
Statut: ppublish

Résumé

Here, we report the synthesis of 3,6,9-trioxaundecan-1-{4-[(2-Chloroethyl)Ethylamino)]-Benzylamino},11-Azide (CEBA). CEBA alkylates the N7 of guanine of DNA thanks its chloroethyl group and can be coupled by a strain-promoted azide-alkyne cycloaddition to an alkynylated molecule. The optimization of the alkylation level of pDNA reveals that the expression of the encoded gene is preserved when it is randomly modified with at most 1 CEBA molecule per 150 bp. We show that the azido group of CEBA allows the linkage via click chemistry of CEBA-pDNA with a fluorophore or a peptide containing a dibenzocyclooctyne (DBCO) function. This new heterobifunctional reagent opens new ways to equip pDNA easily with signal molecules including peptides and nucleic acids without side products providing great interest for non-viral gene therapy.

Identifiants

pubmed: 33812974
pii: S0378-5173(21)00371-9
doi: 10.1016/j.ijpharm.2021.120566
pii:
doi:

Substances chimiques

Alkynes 0
Azides 0
DNA 9007-49-2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

120566

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Haifei Gao (H)

Centre de Biophysique Moléculaire, CNRS UPR4301, Inserm and University of Orléans, F-45071 Orléans cedex 02, France.

Cristine Gonçalves (C)

Centre de Biophysique Moléculaire, CNRS UPR4301, Inserm and University of Orléans, F-45071 Orléans cedex 02, France.

Delphine Maze (D)

Centre de Biophysique Moléculaire, CNRS UPR4301, Inserm and University of Orléans, F-45071 Orléans cedex 02, France.

Chantal Pichon (C)

Centre de Biophysique Moléculaire, CNRS UPR4301, Inserm and University of Orléans, F-45071 Orléans cedex 02, France.

Patrick Midoux (P)

Centre de Biophysique Moléculaire, CNRS UPR4301, Inserm and University of Orléans, F-45071 Orléans cedex 02, France. Electronic address: patrick.midoux@cnrs.fr.

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Classifications MeSH