X-aptamers: a bead-based selection method for random incorporation of druglike moieties onto next-generation aptamers for enhanced binding

Biochemistry. 2012 Oct 23;51(42):8321-3. doi: 10.1021/bi300471d. Epub 2012 Oct 11.


By combining pseudorandom bead-based aptamer libraries with conjugation chemistry, we have created next-generation aptamers, X-aptamers (XAs). Several X-ligands can be added in a directed or random fashion to the aptamers to further enhance their binding affinities for the target proteins. Here we describe the addition of a drug (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), demonstrated to bind to CD44-HABD, to a complete monothioate backbone-substituted aptamer to increase its binding affinity for the target protein by up to 23-fold, while increasing the drug's level of binding 1-million fold.

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

  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / metabolism
  • Base Sequence
  • Hyaluronan Receptors / chemistry
  • Ligands
  • N-Acetylneuraminic Acid / analogs & derivatives
  • N-Acetylneuraminic Acid / chemistry
  • Protein Binding
  • SELEX Aptamer Technique / methods*


  • Aptamers, Nucleotide
  • Hyaluronan Receptors
  • Ligands
  • N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
  • N-Acetylneuraminic Acid