DNA intercalation optimized by two-step molecular lock mechanism
Artikel i vetenskaplig tidskrift, 2016

The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.

Författare

A. A. Almaqwashi

Northeastern University

King Abdulaziz University

Johanna Andersson

Kemi och kemiteknik, Tillämpad kemi, Farmaceutisk teknologi

Per Lincoln

Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

I. Rouzina

Ohio State University

Fredrik Westerlund

Chalmers University of Technology

M. C. Williams

Northeastern University

Scientific Reports

2045-2322 (ISSN)

Vol. 6 37993- 37993

Ämneskategorier

Fysikalisk kemi

Kemi

DOI

10.1038/srep37993