Binding of berberine and sanguinarine with G-quadruplex and duplex DNA revealed by surface-enhanced Raman spectroscopy

Surface-enhanced Raman scattering (SERS) spectroscopy was applied to study binding of natural alkaloid molecules, berberine and sanguinarine, with G-quadruplex (G4) DNA structure. The antiparallel “basket” type G4 structure was obtained upon annealing the human telomeric sequence d[TTAGGG]4 (Tel24) in presence of sodium ions. In addition, the alkaloids selectivity for four-stranded over double-stranded DNA was investigated using calf thymus (ct) DNA. The SERS spectra of the alkaloid ligands, the DNA structures and their complexes in the [ligand]/[DNA] molar ratio of 1/1, 1/3 and 1/6 were obtained upon NIR excitation in a citrate-reduced silver colloid aggregated with sodium sulfate. The same slight decrease in the SERS intensity of berberine bands, regardless of the [ligand]/[ct-DNA] molar ratio, implied very weak interactions with ct-DNA, associated with structurally nonspecific binding of the berberine molecules along the phosphate helix. Moreover, the SERS spectra of sanguinarine with ct-DNA resembled the spectrum of the ligand alone, not indicating any interactions of the sanguinarine molecules with the nucleic acid. On the other hand, notable spectral changes were observed for the complexes of the alkaloid molecules with G-quadruplex, particularly pronounced for the complexes of the [ligand]/[G4] molar ratio 1/3. While significant diminution in the overall SERS intensity indicated stacking of the berberine molecules onto the G4 structure, the upward shift of the guanine bands implied interactions of the sanguinarine molecules with the G4 grooves. The observed SERS spectra clearly pointed to different binding modes of berberine and sanguinarine with antiparallel G-quadruplex as well as to higher affinity of both alkaloid molecules for G-quadruplex over duplex DNA.