+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy



Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy



Nucleic Acids Research 44(9): 3971-3988



There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA-ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed extensively with these methods. Conventional mono-intercalators and bis-intercalators are discussed, followed by unconventional DNA intercalation. We then consider the prospects for using these methods in optimizing conventional and unconventional DNA-intercalating small molecules.

(PDF emailed within 0-6 h: $19.90)

Accession: 058284124

Download citation: RISBibTeXText

PMID: 27085806

DOI: 10.1093/nar/gkw237


Related references

Discriminating small molecule DNA binding modes by single molecule force spectroscopy. Biophysical Journal 82(1 Part 2): 141a-142a, 2002

Multiple unfolding pathways of leucine binding protein (LBP) probed by single-molecule force spectroscopy (SMFS). Journal of the American Chemical Society 135(39): 14768-14774, 2014

Tau aggregation followed by atomic force microscopy and surface plasmon resonance, and single molecule tau-tau interaction probed by atomic force spectroscopy. Journal of Alzheimer's Disease 18(1): 141-151, 2010

Extracting a single polyethylene oxide chain from a single crystal by a combination of atomic force microscopy imaging and single-molecule force spectroscopy: toward the investigation of molecular interactions in their condensed states. Journal of the American Chemical Society 133(10): 3226-3229, 2011

Intramolecular Interactions of Highly π-Conjugated Perylenediimide Oligomers Probed by Single-Molecule Spectroscopy. Journal of Physical Chemistry Letters 5(21): 3895-3901, 2015

Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions. Biochemistry 50(23): 5154-5162, 2011

May the force be with you: unfolding lipid-protein interactions by single-molecule force spectroscopy. Structure 23(4): 612-614, 2016

Structure-property relationship of perylene bisimide macrocycles probed by atomic force microscopy and single-molecule fluorescence spectroscopy. Acs Nano 7(6): 5064-5076, 2013

High density single-molecule-bead arrays for parallel single molecule force spectroscopy. Analytical Chemistry 84(11): 4907-4914, 2012

Analysis of DNA interactions using single-molecule force spectroscopy. Amino Acids 44(6): 1457-1475, 2013

β-Connectin studies by small-angle x-ray scattering and single-molecule force spectroscopy by atomic force microscopy. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics 83(5 Pt 1): 051919, 2011

Single-molecule force spectroscopy of the Aplysia cell adhesion molecule reveals two homophilic bonds. Biophysical Journal 103(4): 649-657, 2013

Homophilic interaction and deformation of E-cadherin and cadherin 7 probed by single molecule force spectroscopy. Archives of Biochemistry and Biophysics 587: 38-47, 2016

Single-molecule force spectroscopy of protein-membrane interactions. Elife 6, 2017

Single-molecule DNA force spectroscopy to probe interactions with the tri-peptide Lys-Trp-Lys. Chemphyschem 12(14): 2545-2548, 2012