Aptamers can discriminate alkaline proteins with high specificity

Hanyang Yu, Bing Jiang, John C. Chaput

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Aptamers are single-stranded nucleic acids that fold into stable three-dimensional structures with ligand binding sites that are complementary in shape and charge to a desired target. Aptamers are generated by an iterative process known as in vitro selection, which permits their isolation from pools of random sequences. While aptamers have been selected to bind a wide range of targets, it is generally thought that these molecules are incapable of discriminating strongly alkaline proteins due to the attractive forces that govern oppositely charged polymers (e.g., polyelectrolyte effect). Histones, eukaryotic proteins that make up the core structure of nucleosomes are attractive targets for exploring the binding properties of aptamers because these proteins have positively charged surfaces that bind DNA through noncovalent sequence-independent interactions. Previous selections by our lab and others have yielded DNA aptamers with high affinity but low specificity to individual histone proteins. Whether this is a general limitation of aptamers is an interesting question with important practical implications in the future development of protein affinity reagents. Here we report the in vitro selection of a DNA aptamer that binds to histone H4 with a K d of 13 nM and distinguishes other core histone proteins with 100 to 480-fold selectivity, which corresponds to a ΔΔG of up to 3.4 kcalmol -1. This result extends our fundamental understanding of aptamers and their ability to fold into shapes that selectively bind alkaline proteins.

Original languageEnglish (US)
Pages (from-to)2659-2666
Number of pages8
JournalChemBioChem
Volume12
Issue number17
DOIs
StatePublished - Nov 25 2011

Keywords

  • Aptamers
  • DNA
  • Histone proteins
  • Molecular evolution

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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