Reversible Regulation of Protein Binding Affinity by a DNA Machine

Chao Zhou†‡, Zhongqiang Yang†, and Dongsheng Liu*†

^† Key Laboratory of Organic Optoelectronics & Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China

^‡ National Center for Nanoscience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, China

J. Am. Chem. Soc., Article ASAP

DOI: 10.1021/ja209590u

Publication Date (Web): January 5, 2011

Copyright © 2012 American Chemical Society

We report a DNA machine that can reversibly regulate target binding affinity on the basis of distance-dependent bivalent binding. It is a tweezer-like DNA machine that can tune the spatial distance between two ligands to construct or destroy the bivalent binding. The DNA machine can strongly bind to the target protein when the ligands are placed at an appropriate distance but releases the target when the bivalent binding is disrupted by enlargement of the distance between the ligands. This “capture–release” cycle could be repeatedly driven by single-stranded DNA without changing the ligands and target protein.