We describe a novel photolithographic approach to the synthesis of peptoids (oligo-N-substituted glycines). This strategy enables the construction of a spatially addressable peptoid microarray, thus providing a potentially powerful tool for the discovery of protein ligands.
We have designed, constructed, and evaluated an automated instrument that has produced high-density arrays with more than 30 000 peptide features within a 1.5 cm(2) area of a glass slide surface. These arrays can be used for high throughput library screening for protein binding ligands, for potential drug candidate molecules, or for discovering biomarkers. The device consists of a novel fluidics system, a relay control electrical system, an optics system that implements Texas Instruments' digital micromirror device (DMD), and a microwave source for accelerated synthesis of peptide arrays. The instrument implements two novel solid phase chemical synthesis strategies for producing peptide and peptoid arrays. Biotin-streptavidin and DNP anti-DNP (dinitrophenol) models of antibody small molecule interactions were used to demonstrate and evaluate the instrument's capability to produce high-density protein detecting arrays. Several screening assay and detection schemes were explored with various levels of efficiency and assays with sensitivity of 10 nM were also possible.
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