Adenine shares the plane with G-quartet detected by surface-enhanced Raman spectroscopy.

DNA G-quadruplexes (G4s) formed by guanine(G)-rich sequences show diversity of structural topologies. The detection of structural details is of great significance for understanding of their functions and for the target drug design, but is very challenging. Herein, we demonstrate that the surface-enhanced Raman spectroscopy (SERS) via Ag IANPs as substrates is able to identify the numbers of Adenine (A) located on the G-quartet of the G4s. Eight G4s are selected for SERS studies. Besides the detection of series of characteristic bands indicating the formation of G4s, the intensity of the band represented A base ring breath (ν, ~733 cm) is observed particularly enhanced when there are A bases coplanar with G-quartet, and which is higher than the intensity of the band corresponding to G base ring breath (ν ~655 cm). Furthermore, the band intensity ratio of ν to ν versus the ratio of the numbers of A on the plane to the sum of numbers of A and G shows very good linear relationship. Thus, based on the band intensities of ν to ν and their ratio in the SERS spectrum, the G-quadruplexes with or without a coplanar A base and numbers of A bases on the plane of G-quartet can be facilely identified. The method is simple, fast, low cost and sensitive to provide particular details of the structure in aqueous solution, therefore, implies widespread applications.