Nanopore detection of guanine derivatives based on vacancy G-quadruplex DNA

Guanine and its derivatives play fundamental roles in many biological processes and their abnormal changes are closely related to diseases. Thus, accurate and sensitive detection of them is beneficial for the early diagnosis and clinical medicine. Herein, a novel nanopore-based sensor is proposed to detection guanine and its derivatives by using a vacancy G-quadruplex (vG4) probe. In this design, the incomplete G-tetrad in vG4 probe can be filled in by guanine derivatives through Hoogsteen hydrogen bond interactions, resulting in stabilization of the G-quadruplex. Based on the different electronic signals between vG4 probe and its binding complexes, the nanopore sensor was able to achieve the detection of six guanine derivatives, including 2΄-dG, Guanine, Guanosine, GMP, GDP and GTP. To demonstrate the analytical performance of the method, a guanine analogue drug was determined as model analyte. The detection limit of acyclovir was 0.0061 μM (3 σ / k ), with a linear range of 0.01 μM – 0.1 μM. This sensing strategy offers a new pathway for label-free detection of nucleobases and derivatives.