Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 30, Pages 12338-12341Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja303218s
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Funding
- NIH [1R15DK081191-01]
- NSF [CHE-1026532]
- NSF Research Experiences for Undergraduates [1004987]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1026532] Funding Source: National Science Foundation
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A 3D folding funnel was proposed in the 1990s to explain the fast kinetics exhibited by a biomacromolecule in presence of seemingly unlimited folding pathways. Over the years, numerous simulations have been performed with this concept; however, experimental verification is yet to be attained even for the simplest proteins. Here, we have used a click chemistry based strategy to introduce six pairs of handles in a human telomeric DNA sequence. A laser-tweezers-based, single-molecule structural fingerprinting on the six inter-handle distances reveals the formation of a hybrid-1 G-quadruplex in the sequence. Kinetic and thermodynamic fingerprinting on the six trajectories defined by each handle-pair depict a 3D folding funnel and a kinetic topology in which the kinetics pertaining to each handle residue is annotated for this G-quadruplex. We anticipate the methods and the concepts developed here are well applicable to other biomacromolecules, including RNA and proteins.
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