Enzymatic synthesis and 19F NMR studies of 2-fluoroadenine-substituted RNA

J Am Chem Soc. 2004 Sep 29;126(38):11776-7. doi: 10.1021/ja047556x.

Abstract

The production of isotopically labeled RNA remains critical to current NMR structural studies. One approach to obtain simple NMR spectra is to label with a nucleus that is not naturally occurring in RNA. Fluorine-19 can serve as a sensitive site-specific probe upon incorporation into RNA. Here we report the efficient in vitro enzymatic synthesis of 2-fluoroadenosine-5'-triphosphate and its incorporation into the HIV-2 transactivation region (TAR) of RNA by DNA template-directed transcription using phage T7 RNA polymerase. We provide unequivocal evidence for this 19F-substituted base analogue capability to selectively interact with uracil, forming 2F-A-U base pairs in RNA. The introduction of a 2-fluoroadenyl substitution is relatively nonperturbing and provides us with uniquely positioned, sensitive NMR reporter groups to monitor structural changes in the local RNA environment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemistry*
  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / chemical synthesis*
  • Adenosine Triphosphate / chemistry
  • Adenylate Kinase / chemistry*
  • Adenylate Kinase / metabolism
  • Creatine Kinase / chemistry*
  • Creatine Kinase / metabolism
  • Fluorine
  • HIV Long Terminal Repeat*
  • HIV-2 / genetics
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Nucleic Acid Conformation
  • RNA, Viral / chemical synthesis*
  • RNA, Viral / chemistry*
  • Thermodynamics

Substances

  • RNA, Viral
  • 2-fluoro-ATP
  • Fluorine
  • 2-fluoroadenine
  • Adenosine Triphosphate
  • Creatine Kinase
  • Adenylate Kinase
  • Adenine