期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 133, 期 20, 页码 7676-7679出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja2017366
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资金
- Tulane Research Enhancement Fund [546738G1]
- Louisiana Board of Regents [LEQSF(2009-12)-RD-A-17]
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 beta-CD/adamantane host-guest interaction to generate a stabilized DNA hairpin (Delta T-m = 17 degrees 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 beta-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.
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