Download Jian Xie is from Hunan province, People`s Republic of China

Jian Xie is from Hunan province, People’s Republic of China. After graduated from the
group of Prof. Zhitang Huang in Institute of Chemistry, Chinese Academy of Sciences in
2000, he joined Prof. Christopher T. Seto’s group in Department of Chemistry, Brown
University, working on the synthesis and properties study of Protein Tyrosine
Phosphatase inhibitors.
It’s well known that protein tyrosine phosphatases (PTPase) play very important
roles in the cell activities. Opposing actions of PTPase and PTKase (protein tyrosine
kinase) regulate the reversible tyrosine phosphorylation and dephosphorylation of
proteins, which subsequently control the cell growth, mitogenesis, motility, cell-cell
interaction, metabolism, gene transcription and the immune response, etc. Defective or
inappropriate PTPase operation can result in wide spread diseases such as diabetes,
cancers and immune dysfunctions. It has been found out that overexpressed PTPases such
as PTP1B might induce Type II diabetes. Yersinia PTPase was found to be the important
virulent determinant in the Black Death, or the Bubonic plague. Another interesting
example is PTP1B-deficient mice showed increased insulin sensitivity and obesity
resistance. All these studies suggest that inhibition against PTPases is an interesting drug
target.
Our previous research found that -ketoacid can work as the mimic of the phosphate.
Recently it has been reported that there are two binding sites in the PTPase for substrate.
This instantly suggests a method of improving the inhibitor binding affinity by
incorporating two aryl -ketoacid moieties into one single inhibitor structure. Jian Xie is
working on library synthesis based on diamine backbone. Assay on crude inhibitors
affords a relatively quick screening method.
Latest results show that squaric acid is a new mimic of phosphate group.