Evolution and protein packaging of small-molecule RNA aptamers

ACS Nano. 2011 Oct 25;5(10):7722-9. doi: 10.1021/nn2006927. Epub 2011 Sep 7.

Abstract

A high-affinity RNA aptamer (K(d) = 50 nM) was efficiently identified by SELEX against a heteroaryldihydropyrimidine structure, chosen as a representative drug-like molecule with no cross reactivity with mammalian or bacterial cells. This aptamer, its weaker-binding variants, and a known aptamer against theophylline were each embedded in a longer RNA sequence that was encapsidated inside a virus-like particle by a convenient expression technique. These nucleoprotein particles were shown by backscattering interferometry to bind to the small-molecule ligands with affinities similar to those of the free (nonencapsidated) aptamers. The system therefore comprises a general approach to the production and sequestration of functional RNA molecules, characterized by a convenient label-free analytical technique.

Publication types

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

MeSH terms

  • Allolevivirus / genetics
  • Allolevivirus / metabolism
  • Aptamers, Nucleotide / genetics
  • Aptamers, Nucleotide / metabolism*
  • Base Sequence
  • Capsid Proteins / chemistry*
  • Capsid Proteins / metabolism*
  • Inverted Repeat Sequences / genetics
  • Ligands
  • Molecular Sequence Data
  • Pyrimidines / chemistry
  • Pyrimidines / metabolism
  • SELEX Aptamer Technique / methods*

Substances

  • Aptamers, Nucleotide
  • Capsid Proteins
  • Ligands
  • Pyrimidines