Foldamer Nanotubes Mediated Label-Free Detection of Protein-Small Molecule Interactions

Development of miniaturized lab-on-chip devices for the detection of rapid and specific small molecule-protein binding interactions at very low concentrations holds significant importance in drug discovery and biomedical applications. Here, the label-free detection of small molecule-protein interactions is reported on the surface functionalizable nanotubes of α,γ-hybrid peptide helical foldamers using nanoscale capacitance and impedance spectroscopy. The 12-helix conformation of the α,γ-hybrid peptide observed in the single crystals, self-assembled into nanotubes in an aqueous environment with exposed cysteine thiols for small molecule conjugation. The binding of streptavidin to the covalently linked biotin on the surface of nanotubes was detected at the picomolar concentrations. No change in the capacitance and impedance were observed in the absence of either immobilized biotin or protein streptavidin. The functionalizable hybrid peptide nanotubes reported here pave the way for the label-free detection of various small molecule protein interactions at very low concentrations.