Revealing the specific interactions between G-quadruplexes and ligands by surface-enhanced Raman spectroscopy

G-quadruplexes (G4s) regulate a variety of physiological functions related to diseases and life elongation. Therefore, G4 binding ligands, such as potential drugs in gene therapy or molecular probes for biosensing and bioimaging, are receiving extensive attention. However, identifying the binding modes and interaction details between G4s and their ligands is very challenging. Recently, we demonstrated that surface-enhanced Raman scattering (SERS) could quickly provide structural details of G4s. Herein, three G4 binding ligands that interact with the separated G4 in different ways are selected as models to evaluate the feasibility of SERS analysis in studying G4-ligand interactions. As a result, adequate SERS information indicating the specific interactions between the G4s and the ligand is obtained via using Ag IANPs as substrates. The results demonstrate that SERS is a powerful tool for revealing comprehensive and specific ligand-DNA interactions with advantages such as speed, simplicity, trace sample amount requirement, and compatibility with aqueous samples.