Molecular Diversity

, Volume 4, Issue 2, pp 75–89

The limits of specificity: An experimental analysis with RNA aptamers to MS2 coat protein variants

  • Ichiro Hirao
  • Marc Spingola
  • David Peabody
  • Andrew D. Ellington
Article

DOI: 10.1023/A:1026401917416

Cite this article as:
Hirao, I., Spingola, M., Peabody, D. et al. Mol Divers (1998) 4: 75. doi:10.1023/A:1026401917416

Abstract

It has been hypothesized that selections for aptamers with high affinity for a given target molecule will of necessity identify aptamers that have high specificity for that target. We have attempted to assess this hypothesis by selecting aptamers that can bind to MS2 coat protein or to single- or double-substitution variants of the coat protein. Some aptamers selected to bind MS2 coat protein or its variants were mildly specific for their cognate targets, discriminating by two- to fourfold against closely related proteins. Specificity determinants on both the coat proteins and the aptamers could be identified. However, many aptamers could readily bind to each of the different coat proteins. The identification of such aptamer 'generalists’ belies the proposed relationship between the affinities and specificities of selected RNA ligands. These results imply that, while aptamers may not finely discriminate between closely related targets, neither will their binding be negated by mutations in targets. Aptamer pharmaceuticals may therefore better resist the evolution of resistance.

aptamercoat proteinin vitro selectionmolecular recognitionMS2SELEX

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Ichiro Hirao
    • 1
  • Marc Spingola
    • 2
  • David Peabody
    • 2
  • Andrew D. Ellington
    • 1
  1. 1.Department of Chemistry, ICMB A4800University of Texas at AustinAustinU.S.A
  2. 2.Department of Molecular Genetics and MicrobiologyUniversity of New Mexico School of MedicineAlbuquerqueU.S.A