Journal
NATURE NANOTECHNOLOGY
Volume 14, Issue 10, Pages 988-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41565-019-0542-7
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Funding
- Labex NanoSaclay
- Idex Paris-Saclay
- PSL University
- Labex Memolife
- PSL-Valorisation
- National Science Foundation
- China Scholarship Council
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The residence time of a drug on its target has been suggested as a more pertinent metric of therapeutic efficacy than the traditionally used affinity constant. Here, we introduce junctured-DNA tweezers as a generic platform that enables real-time observation, at the single-molecule level, of biomolecular interactions. This tool corresponds to a double-strand DNA scaffold that can be nanomanipulated and on which proteins of interest can be engrafted thanks to widely used genetic tagging strategies. Thus, junctured-DNA tweezers allow a straightforward and robust access to single-molecule force spectroscopy in drug discovery, and more generally in biophysics. Proof-of-principle experiments are provided for the rapamycin-mediated association between FKBP12 and FRB, a system relevant in both medicine and chemical biology. Individual interactions were monitored under a range of applied forces and temperatures, yielding after analysis the characteristic features of the energy profile along the dissociation landscape.
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