Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors.


Journal

Biochemistry
ISSN: 1520-4995
Titre abrégé: Biochemistry
Pays: United States
ID NLM: 0370623

Informations de publication

Date de publication:
22 09 2020
Historique:
pubmed: 29 8 2020
medline: 17 3 2021
entrez: 29 8 2020
Statut: ppublish

Résumé

There are few methods available for the rapid discovery of multitarget drugs. Herein, we describe the template-assisted, target-guided discovery of small molecules that recognize d(CTG) in the expanded d(CTG·CAG) sequence and its r(CUG) transcript that cause myotonic dystrophy type 1. A positive cross-selection was performed using a small library of 30 monomeric alkyne- and azide-containing ligands capable of producing >5000 possible di- and trimeric click products. The monomers were incubated with d(CTG)

Identifiants

pubmed: 32856901
doi: 10.1021/acs.biochem.0c00472
pmc: PMC7793557
mid: NIHMS1654201
doi:

Substances chimiques

Small Molecule Libraries 0
RNA 63231-63-0
DNA 9007-49-2

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3463-3472

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM103399
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069645
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM070421
Pays : United States

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Auteurs

Lauren D Hagler (LD)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Long M Luu (LM)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Marco Tonelli (M)

National Magnetics Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

JuYeon Lee (J)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Samuel M Hayes (SM)

Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

Sarah E Bonson (SE)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

J Ignacio Vergara (JI)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Samuel E Butcher (SE)

Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

Steven C Zimmerman (SC)

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

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