A pH and Mg2+-Responsive Molecular Switch Based on a Stable DNA Minidumbbell Bearing 5' and 3'-Overhangs

Jiacheng Zhang; Yang Wang; Liqi Wan; Yuan Liu; Jie Yi; Sik Lok Lam; Pei Guo

doi:10.1021/acsomega.1c04346

A pH and Mg²⁺-Responsive Molecular Switch Based on a Stable DNA Minidumbbell Bearing 5' and 3'-Overhangs

ACS Omega. 2021 Oct 14;6(42):28263-28269. doi: 10.1021/acsomega.1c04346. eCollection 2021 Oct 26.

Authors

Jiacheng Zhang¹, Yang Wang¹, Liqi Wan², Yuan Liu³, Jie Yi¹, Sik Lok Lam², Pei Guo¹

Affiliations

¹ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China.
² Department of Chemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong, China.
³ South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China.

Abstract

Minidumbbell (MDB) is a non-B DNA structure of which the thermodynamic stability is sensitive to a chemical environment such as pH, serving as a potential structural motif in constructing DNA-based molecular switches. This work aims to design thermodynamically stable MDB structures bearing 5' and 3'-overhanging deoxyribonucleotides in order to examine the possibility of MDB to be functionalized. Via making use of 5-methylcytosine and adjusting the pH of solution to be acidic, MDBs bearing 1-nucleotide (nt) or 2-nt overhanging residues at the 5' and 3'-ends have been obtained. Based on one of the new MDB sequences, we have designed a molecular switch that could respond to dual inputs of pH and Mg²⁺. The MDB strand and its partner strand formed a duplex (the "ON" state) upon inputting pH 7 and Mg²⁺, whereas the duplex dissociated to restore the MDB structure (the "OFF" state) upon inputting pH 5 and EDTA. The demonstration on the ability of MDB to sustain 5' and 3'-overhanging residues and the construction of a pH and Mg²⁺-responsive molecular switch will extend the application of MDB structures in dynamic DNA nanotechnology.