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Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold

Publication ,  Journal Article
Donlic, A; Morgan, BS; Xu, JL; Liu, A; Roble, C; Hargrove, AE
Published in: Angewandte Chemie
October 2018

Structural studies of the 3′‐end of the oncogenic long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) confirmed a unique triple‐helix structure. This structure enables accumulation of the transcript, and high levels of MALAT1 are found in several cancers. Here, we synthesize a small molecule library based on an RNA‐binding scaffold, diphenylfuran (DPF), screen it against a variety of nucleic acid constructs, and demonstrate for the first time that the MALAT1 triple helix can be selectively targeted with small molecules. Computational analysis revealed a trend between subunit positioning and composition on DPF shape and intramolecular interactions, which in turn generally correlated with selectivity and binding strengths. This work thus provides design strategies toward chemical probe development for the MALAT1 triple helix and suggests that comprehensive analyses of RNA‐focused libraries can generate insights into selective RNA recognition.

Duke Scholars

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Published In

Angewandte Chemie

DOI

EISSN

1521-3757

ISSN

0044-8249

Publication Date

October 2018

Volume

130

Issue

40

Start / End Page

13426 / 13431

Publisher

Wiley

Related Subject Headings

  • Organic Chemistry
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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Chicago
ICMJE
MLA
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Donlic, A., Morgan, B. S., Xu, J. L., Liu, A., Roble, C., & Hargrove, A. E. (2018). Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold. Angewandte Chemie, 130(40), 13426–13431. https://doi.org/10.1002/ange.201808823
Donlic, Anita, Brittany S. Morgan, Jason L. Xu, Anqi Liu, Carlos Roble, and Amanda E. Hargrove. “Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold.” Angewandte Chemie 130, no. 40 (October 2018): 13426–31. https://doi.org/10.1002/ange.201808823.
Donlic A, Morgan BS, Xu JL, Liu A, Roble C, Hargrove AE. Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold. Angewandte Chemie. 2018 Oct;130(40):13426–31.
Donlic, Anita, et al. “Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold.” Angewandte Chemie, vol. 130, no. 40, Wiley, Oct. 2018, pp. 13426–31. Crossref, doi:10.1002/ange.201808823.
Donlic A, Morgan BS, Xu JL, Liu A, Roble C, Hargrove AE. Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold. Angewandte Chemie. Wiley; 2018 Oct;130(40):13426–13431.
Journal cover image

Published In

Angewandte Chemie

DOI

EISSN

1521-3757

ISSN

0044-8249

Publication Date

October 2018

Volume

130

Issue

40

Start / End Page

13426 / 13431

Publisher

Wiley

Related Subject Headings

  • Organic Chemistry
  • 34 Chemical sciences
  • 03 Chemical Sciences