SERS and DFT Study of Noble-Metal-Anchored Cys-Trp/Trp-Cys Dipeptides: Influence of Main-Chain Direction and Terminal Modifications

Tiny changes in the covalent structure of a noble-metal-anchored peptide may affect its surface-enhanced Raman scattering (SERS) signature. While SERS spectra of Cys-Trp peptides are dominated by the bands arising from the aromatic Trp side chain, a thorough study of the impact of modifications in SERS-silent regions concerning such dipeptides was yet to be performed. Thus, here we conduct an extensive SERS study of a series of Cys- and Trp-containing dipeptides, varying both the main-chain direction (Cys-Trp/Trp-Cys) and the presence of typical covalent modifications at N- and C-termini (acetylation/amidation). We use three different SERS-active substrates: oxidation–reduction cycling-roughened silver (Ag ORC), gold (Au ORC), and chemically synthesized colloidal silver nanoparticles (Ag NPs). Interpretation of the experimental data was aided with density functional theory (DFT) calculations. Potential energy distribution (PED) analysis was used for the assignment of dipeptide vibrational bands. IR and normal Raman spectra were also examined to get a complete vibrational analysis. This work may be considered the first report on the effect of terminal group modification and reversing the peptide sequence on the adsorptive behavior of dipeptide on silver and gold surface studied by SERS spectroscopy, supported by full vibrational assignment by means of the DFT method.