Reversible Photocontrol of Thrombin Activity by Replacing Loops of Thrombin Binding Aptamer using Azobenzene Derivatives

April 9, 2019

Title

Reversible Photocontrol of Thrombin Activity by Replacing Loops of Thrombin Binding Aptamer using Azobenzene Derivatives

Author

Mengwu Mo, Dejia Kong, Heming Ji, Dao Lin, XinJing Tang, Zhenjun Yang, Yujian He, Li Wu

Year

2018

Journal

Bioconjugate Chemistry

Abstract

The photoisomerization of azobenzenes provides a general means for the photocontrol of many important biomolecular structure and organismal function. For temporal and spatial control activity of thrombin binding aptamer (TBA) by light, azobenzene derivatives were carefully selected as light-triggered molecular switches to replace TT loops and TGT loop of TBA to reversibly control enzyme activity. These molecules interconverted between the trans and cis states under alternate UV and visible light irradiation, which consequently triggered reversible formation of G-quadruplex morphology. In addition, we investigated the impact of three azobenzene derivatives on stability, thrombin binding ability and anticoagulant properties. The result showed that 4,4’-bis(hydroxymethyl)azobenzene at TGT loop position significantly photoregulated affinity to thrombin and blood clotting in human plasma, which provided a successful strategy to control blood clotting in human plasma and a further evidence for design of TBA analogues with pivotal positions of modifications.

Instrument

J-815

Keywords

Circular dichroism, DNA structure, Thermal stability, Thermodynamics, Biochemistry