Natural products are rich sources for potential drugs. To accelerate drug discovery from natural products, it is imperative to identify their molecular targets, and mechanistically elucidate their bioavailability, toxicity, and therapeutic effects. However, there remain several challenges in the field. Among them, there is currently no technical platform that could perform mechanistic studies from the """"""""hits"""""""" to """"""""leads"""""""" using the small volumes of samples that are typically encountered in quantitative high-throughput screening (qHTS). In response to RFA- AT-14-001, Newomics Inc. proposes to develop a multi-omics platform for high-throughput and high-content bioassays of natural products. The core technology will be based on Newomics'breakthrough silicon- microfluidic-chip, the multinozzle emitter array chip (MEA chip-2012 R&D100 award), which enables liquid chromatography-nanoelectrospray ionization mass spectrometry (LC-nanoESI/MS)-based, highly sensitive, highly specific, high-throughput, and multiplex measurements of multiclass analytes (peptides, proteins, and metabolites) at the Omics level, from small volumes of samples. In this project, we will incorporate multiple Omics capabilities, including top-down proteomics, bottom-up proteomics, and metabolomics, on a single MEA chip, in a high-throughput and multiplex format. We will demonstrate proof-of-principle applications of our multi- omics platform in the Phase I.
In Aim 1, we will develop the ESI-MS assays to screen the interactions between purified human serum albumin (HSA), the most abundant protein and the key carrier of endogenous and exogenous substances in the plasma, and a selected number of natural products.
In Aim 2, we will develop the Omics-based assays for probing interactions between HSA in whole blood and libraries of natural products with different complexity. Once developed, Newomics'MEA chip may become a universal platform for high- throughput identification of molecular targets of natural products in the blood or other tissues, and lay a new foundation for drug discovery and development.
Cutting-edge technologies enable breakthroughs in biomedical research. Developments of innovative and integrated mass spectrometry-based microfluidic chips will accelerate the high-throughput identification and validation of molecular targets of natural products, thereby contributing to new drug discovery and development.
| Chen, Yuchao; Mao, Pan; Wang, Daojing (2018) Quantitation of Intact Proteins in Human Plasma Using Top-Down Parallel Reaction Monitoring-MS. Anal Chem 90:10650-10653 |
| Han, Yan; Zhao, Jinghua; Huang, Ruili et al. (2018) Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells. J Proteome Res 17:579-589 |
| Gil, Geuncheol; Mao, Pan; Avula, Bharathi et al. (2017) Proteoform-Specific Protein Binding of Small Molecules in Complex Matrices. ACS Chem Biol 12:389-397 |
| Mao, Pan; Wang, Daojing (2015) Biomonitoring of perfluorinated compounds in a drop of blood. Environ Sci Technol 49:6808-14 |
