The SERS spectrum of DNA is strongly dominated by the strong spectral feature of adenine at 736 cm(-1); the presence of adenine can serve as an endogenous marker for the label-free SERS-based detection of DNA hybridization when the probe DNA sequence is adenine-free. The substitution of 2-aminopurine for adenine on the probe DNA sequence enables the detection of a target sequence using SERS, upon hybridization of the target with the 2-AP-substituted probe DNA sequence.