The study of protein phosphorylation (Figure 1) is called phosphoproteomics and is one of the important post-translational modification (PTM) methods in protein research, which mainly occurs on serine, threonine and tyrosine residues. This kind of PTM plays an important role in almost all cell signal transduction pathways, and at least 1/3 are closely related to cancer, metabolism and other diseases of greatest concern to humans.

Figure 1 Protein (kinase) phosphorylation process

However, phosphoproteome analysis is extremely challenging, with low-abundance phosphopeptides coexisting among high-abundance (millions of) unmodified peptides. Currently, highly specific phosphopeptide enrichment (Figure 2) is a necessary condition to achieve phosphoproteomic analysis.

Figure 2 Phosphoproteomic analysis process

Researcher Ye Mingliang's team at the Dalian Institute of Chemical Physics, Chinese Academy of Sciences discovered for the first time the highly specific interaction between phosphopeptides and titanium ions. Based on the new mechanism, they developed a new generation of fixed metal ion affinity chromatography methods, new technologies, and new materials - Ti-IMAC.

The ability to identify protein phosphorylation is more than 3 times higher than that of conventional immobilized metal ion affinity chromatography (Fe3+-IMAC) [1-2]; compared with TiO2, it can be improved by about 30%, and the enrichment specificity can reach 95% [3 ];
Compared with conventional phosphopeptide enrichment materials such as TiO2, phosphopeptide enrichment efficiency is higher [4].
Due to the excellent enrichment performance of Ti-IMAC materials, it has received widespread attention and has been recognized by well-known universities, scientific research institutes and bio-tech companies at home and abroad.

Figure 3 Structural diagram of phosphopeptide M：Ti^{4+ [1-2]}

<sup>application
1. Application to large-scale analysis of human liver phosphoproteome
The largest phosphorylation site data set in human liver tissue was obtained [5][5]</sup>

^{2. Established a highly specific enrichment method for tyrosine phosphorylated peptides
Achieved deep coverage identification of human tyrosine phosphorylation sites [6][6]}

<sup>Researcher Ye Mingliang's scientific research results have been transformed, and Bailingwei exclusively provides a new generation of phosphopeptide enrichment material - Ti-IMAC.

Researcher Ye Mingliang is mainly engaged in research work on biological separation analysis. He has developed a series of new technologies and methods for proteomics analysis, especially in protein post-translational modification and drug target identification, and has established a number of new analytical methods at the international level. Published more than 200 papers in SCI journals such as Nat. Methods, Nat. Chem. Biol., PNAS, Nat. Commun., Nat. Protoc., JACS, Angew. Chem. Int. Ed, Anal. Chem., etc., according to Google Scholar, cited more than 14,000 times. He has won the President’s Special Scholarship Award of the Chinese Academy of Sciences, the Liaoning Provincial Natural Science Award twice, and the National Natural Science Second Prize once. He has successively presided over projects such as the NSFC Outstanding Youth Fund, National Key R&D Program Key Projects, NSFC Key Projects, Ministry of Science and Technology Innovative Method Projects, and National Major Scientific Research Plan Projects.</sup>

^{2749380
Monodisperse immobilized affinity chromatography microspheres
CAE-Ti-IMAC, 100%
Particle size: ~10μm
Enrichment method: solution method}

^{2749381
Solid phase extraction immobilized affinity chromatography microspheres
SPE-Ti-IMAC, 100%
Particle size: 40-100μm
Enrichment method: solution method/Tip column method}

^References

1. Zhou, H., Ye, M., Dong, J. et al. Nat Protoc.2013, 461–480.
2. Zhou H, Ye M, Dong J, Han G, Jiang X, Wu R, Han F. Journal of Proteome Research. 2008, 7, 3957-3967.
3. Yao Y, Dong J, Dong M, Liu F, Wang Y, Mao J, Ye M, Zou H. J. Chromatogr. A. 2017, 1498, 22–28.
4. Zhou, Houjiang,Low, Teck Y.,Hennrich, Marco L.,et al. Molecular & Cellular Proteomics. 2011,10(10):1.
5. Bian Y, et al. J. Proteomics. 2014, 96, 253-262.
6. Nat. Chem. Biol., 2016, 12, 959-968.