title: Protein-binding molecular switches via host-guest stabilized DNA hairpins.
abstract: Molecular switches, with target protein-binding activity controlled by prior binding to specific input stimuli, are ubiquitously used in Nature. However, the emulation of such responsive systems, especially in a de novo fashion, remains a significant challenge. Herein, we disclose a strategy that harnesses an intramolecular β-CD/adamantane host-guest interaction to generate a stabilized DNA hairpin (ΔT(m) = 17 °C) that undergoes an input oligonucleotide (ODN)-selective structural transformation from a stem-loop conformation to a duplex. This ODN-induced conformational switch allows for the transition from an inactive state (wherein the adamantane protein-binding headgroup is encapsulated) to an activated protein-binding complex, with a freely accessible adamantane moiety. Given that hairpin domains can be readily modulated to be responsive to alternative ODN triggering sequences and that encapsulating macrocycles, such as β-CD, are good hosts for a number of protein-binding small molecules, this strategy may furnish a general method to develop ODN-responsive protein-binders.
authors.affiliation: Department of Chemistry, Tulane University, 2015 Percival Stern Hall, New Orleans, Louisiana 70118, USA.
authors.forename: D Calvin
authors.initials: DC
authors.lastname: Harris
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Saks
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Jayawickramarajah
mesh_terms: D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D009690:Nucleic Acid Conformation; D011485:Protein Binding
chemical_list: D017931:DNA Primers; D004247:DNA