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Application of NMR SHAPES screening to an RNA target

Academic Article
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Overview

authors

  • Johnson, Erik C.
  • Feher, V. A.
  • Peng, J. W.
  • Moore, J. M.
  • Williamson, James

publication date

  • December 2003

journal

  • Journal of the American Chemical Society  Journal

abstract

  • Several NMR screening techniques have been developed in recent years to aid in the identification of lead drug compounds. These NMR methods have traditionally been used for protein targets, and here we examine their applicability for an RNA target. We used the SHAPES compound library to test three different NMR screening methodologies: the saturation transfer difference (STD), the 2D trNOESY, and the WaterLOGSY experiments. We found that the WaterLOGSY experiment was the most sensitive method for our RNA target, the P4P6 domain of the Tetrahymena thermophila Group I intron. Using the WaterLOGSY experiment, we found that 23 of the 112 SHAPES compounds interact with P4P6. To identify which of these 23 hits bind through nonspecific interactions, we counterscreened with a linear duplex RNA control and identified one of the SHAPES compounds as interacting with P4P6 specifically. We thus demonstrated that the WaterLOGSY experiment in combination with the SHAPES compound library can be used to efficiently find RNA binding lead compounds.

subject areas

  • Animals
  • Introns
  • Nuclear Magnetic Resonance, Biomolecular
  • RNA, Protozoan
  • Tetrahymena
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja037499s

PubMed ID

  • 14677945
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Additional Document Info

start page

  • 15724

end page

  • 15725

volume

  • 125

issue

  • 51

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