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A G‐Quadruplex Aptamer Inhibits the Phosphatase Activity of Oncogenic Protein Shp2 in vitro
Author(s) -
Hu Jia,
Wu Jie,
Li Cong,
Zhu Ling,
Zhang Wei Yun,
Kong Guiping,
Lu Zhongxian,
Yang Chaoyong James
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000470
Subject(s) - aptamer , protein tyrosine phosphatase , g quadruplex , phosphatase , in vitro , biochemistry , dna , biology , chemistry , recombinant dna , microbiology and biotechnology , target protein , tyrosine , phosphorylation , gene
Abstract Shp2 is a member of the protein tyrosine phosphatase (PTP) family, which regulates a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Using a recombinant Shp2‐GST protein as the target and GST as a counter target, we have identified two classes of single‐stranded DNA aptamers that selectively bind to Shp2 with a K d in the nanomolar range. Structural studies of the most abundant sequence in the enriched library, HJ24, revealed a parallel G‐quadruplex as the core binding domain. Furthermore, this aptamer was found to be an effective inhibitor of Shp2 phosphatase, an effect which was readily reversed by using the cDNA of HJ24. In view of these characteristics, this aptamer has the potential to be used for further development of Shp2 assays and therapeutics for the treatment of Shp2‐dependent cancers and other diseases.