Towards DNA-Encoded Micellar Chemistry: DNA-Micelle Association and Environment Sensitivity of Catalysis.

DNA conjugates copolymers heterocycle synthesis micellar catalysis partitioning

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
12 Jul 2021
Historique:
received: 17 03 2021
pubmed: 13 5 2021
medline: 16 7 2021
entrez: 12 5 2021
Statut: ppublish

Résumé

The development of DNA-compatible reaction methodologies is a central theme to advance DNA-encoded screening library technology. Recently, we were able to show that sulfonic acid-functionalized block copolymer micelles facilitated Brønsted acid-promoted reactions such as the Povarov reaction on DNA-coupled starting materials with minimal DNA degradation. Here, the impact of polymer composition on micelle shape, and reaction conversion was investigated. A dozen sulfonic acid-functionalized block copolymers of different molar mass and composition were prepared by RAFT polymerization and were tested in the Povarov reaction, removal of the Boc protective group, and the Biginelli reaction. The results showed trends in the polymer structure-micellar catalytic activity relationship. For instance, micelles composed of block copolymers with shorter acrylate ester chains formed smaller particles and tended to provide faster reaction kinetics. Moreover, fluorescence quenching experiments as well as circular dichroism spectroscopy showed that DNA-oligomer-conjugates, although highly water-soluble, accumulated very effectively in the micellar compartments, which is a prerequisite for carrying out a DNA-encoded reaction in the presence of polymer micelles.

Identifiants

pubmed: 33979454
doi: 10.1002/chem.202100980
pmc: PMC8361662
doi:

Substances chimiques

Micelles 0
Polymers 0
DNA 9007-49-2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

10048-10057

Subventions

Organisme : EFRE-NRW
ID : EFRE-NRW-funded Patent Validation Grant
Organisme : EFRE-NRW
ID : EFRE-NRW-funded Drug Discovery Hub Dortmund (DDHD)
Organisme : DFG
ID : EXC 2033 - 390677874 - RESOLV

Informations de copyright

© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

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Auteurs

Mateja Klika Škopić (M)

Medicinal Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

Christian Gramse (C)

Polymer Hybrid Systems, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

Rosario Oliva (R)

Physical Chemistry - Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 4a, 44227, Dortmund, Germany.

Sabrina Pospich (S)

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227, Dortmund, Germany.

Laura Neukirch (L)

Medicinal Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

Magiliny Manisegaran (M)

Physical Chemistry - Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 4a, 44227, Dortmund, Germany.

Stefan Raunser (S)

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227, Dortmund, Germany.

Roland Winter (R)

Physical Chemistry - Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 4a, 44227, Dortmund, Germany.

Ralf Weberskirch (R)

Polymer Hybrid Systems, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

Andreas Brunschweiger (A)

Medicinal Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

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Classifications MeSH