Title of funded project：Smart enrichment materials for tyrosine phosphorylated peptides

Funding agency：National Natural Science Foundation of China

Grant number：22174138

Total funding amount：CNY 600,000

Tyrosine phosphorylation and its kinases participate in the regulation of many important biological processes, including cell proliferation, cycle progression, migration, apoptosis, angiogenesis, gene transcription, and metabolic reactions. In particular, they are key factors in cell signal transduction and play key roles in the occurrence and development of tumors. As of 2019, the US FDA has approved 52 small molecule protein kinase inhibitors, of which 63% are tyrosine kinase inhibitors. The large-scale identification of protein tyrosine phosphorylation by mass spectrometry can obtain information about its corresponding kinase activity and related signal pathways, which is of great significance for the development and clinical application of antitumor drugs. However, the mass spectrometry analysis of tyrosine phosphorylated proteomics encounter many challenges, and there is an urgent need to develop advanced enrichment materials and technologies that can specifically recognize tyrosine phosphorylated peptides. This project proposes to build a series of smart polymers based on guanidine molecules by learning the binding sites of the SH2 superbinder core, and develop them as chromatographic enrichment materials for efficient enrichment and separation of tyrosine phosphorylated peptides. The integration of new materials and the development of methodology will help to dynamically and holistically identify the changes in the types, quantities and structures of proteins kinases in the course of disease occurrence, discovering disease diagnosis, prognostic markers and drug treatment targets.