Alkyne-Functionalized Coumarin Compound for Analytic and Preparative 4-Thiouridine Labeling

Bioconjug Chem. 2017 Apr 19;28(4):1123-1134. doi: 10.1021/acs.bioconjchem.7b00035. Epub 2017 Mar 15.

Abstract

Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on post-transcriptional modification. This work focuses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA and is used as a metabolic label and for cross-linking purposes in eukaryotic RNA. A newly designed coumarin compound named 4-bromomethyl-7-propargyloxycoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via "click chemistry", thereby offering a wide range of preparative and analytical options. We applied PBC to quantitatively monitor the metabolic incorporation of s4U as a label into RNA and for site-specific introduction of a fluorophore into bacterial tRNA at position 8, allowing the determination of its binding constant to an RNA-modification enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels / chemical synthesis
  • Alkynes / chemistry
  • Binding Sites
  • Click Chemistry
  • Coumarins / chemistry*
  • Protein Binding
  • RNA Processing, Post-Transcriptional
  • RNA, Bacterial / metabolism*
  • Staining and Labeling / methods*
  • Thiouridine / chemistry

Substances

  • Affinity Labels
  • Alkynes
  • Coumarins
  • RNA, Bacterial
  • Thiouridine
  • coumarin