Rapid identification of metal-binding peptoid oligomers by on-resin x-ray fluorescence screening

N-Substituted glycine peptoid oligomers have recently attracted attention for their metal binding capabilities. Due to their efficient synthesis on solid phase, peptoids are well suited for generation of compound libraries, followed by screening for molecular recognition and other diverse functional attributes. Ideally, peptoids could be simultaneously screened for binding to a number of metal species. Here, we demonstrate the use of bench-top X-ray fluorescence (XRF) instrumentation to screen rapidly, on solid support, a library of peptoid oligomers incorporating metal-binding functionalities. A subset of the peptoid sequences exhibited significant metal binding capabilities, including a peptoid pentamer and a nonamer that were shown to selectively bind nickel. The binding capabilities were validated by colorimetric assay and by depletion of Ni²⁺ ion concentration from solution, establishing benchtop XRF as a rapid, practicable high-throughput screening technique for peptoid oligomers. This protocol will facilitate discovery of metallopeptoids with unique material properties.