Kinetics of Toehold-Mediated DNA Strand Displacement Depend on FeII4L4 Tetrahedron Concentration.

Jinbo Zhu,Filip Bošković,Ulrich F Keyser,Bao-Nguyen T Nguyen,Jonathan R Nitschke

doi:10.1021/acs.nanolett.0c04125

Jinbo Zhu, Filip Bošković + Show 3 more

Open Access

https://doi.org/10.1021/acs.nanolett.0c04125

Copy DOI

Journal: Nano letters	Publication Date: Jan 28, 2021
Citations: 18	License type: CC BY 4.0

Affiliation: University of Cambridge

Abstract

The toehold-mediated strand displacement reaction (SDR) is a powerful enzyme-free tool for molecular manipulation, DNA computing, signal amplification, etc. However, precise modulation of SDR kinetics without changing the original design remains a significant challenge. We introduce a new means of modulating SDR kinetics using an external stimulus: a water-soluble FeII4L4 tetrahedral cage. Our results show that the presence of a flexible phosphate group and a minimum toehold segment length are essential for FeII4L4 binding to DNA. SDRs mediated by toehold ends in different lengths (3–5) were investigated as a function of cage concentration. Their reaction rates all first increased and then decreased as cage concentration increased. We infer that cage binding on the toehold end slows SDR, whereas the stabilization of intermediates that contain two overhangs accelerates SDR. The tetrahedral cage thus serves as a versatile tool for modulation of SDR kinetics.

Highlights

The toehold-mediated strand displacement reaction (SDR) is a powerful enzyme-free tool for molecular manipulation, DNA computing, signal amplification, etc
A means to precisely adjust the kinetics of toehold mediated SDR without changing the original design, DNA sequence, and structure would be of value to the community
Our previous work has shown that water-soluble tetrahedral cage FeII4L4 binds to nonpaired bases in DNA structures.[38]

Summary

Corresponding Authors

Keyser − Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom; Letter orcid.org/0000-0003-3188-5414; Email: ufk20@ cam.ac.uk Jonathan R. Nitschke − Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; orcid.org/0000-0002-4060-5122; Email: jrn34@ cam.ac.uk. Jinbo Zhu − Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom; orcid.org/00000003-4935-825X. Filip Bosǩ ović − Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom; orcid.org/0000-0001-7663-2408. Nguyen − Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.

■ ACKNOWLEDGMENTS

■ REFERENCES