title: A G-quadruplex aptamer inhibits the phosphatase activity of oncogenic protein Shp2 in vitro.
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.
authors.affiliation: State Key Laboratory for Physical Chemistry of Solid Surfaces, The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Wei Yun
authors.initials: WY
authors.lastname: Zhang
authors.forename: Guiping
authors.initials: G
authors.lastname: Kong
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Lu
authors.forename: Chaoyong James
authors.initials: CJ
authors.lastname: Yang
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D054856:G-Quadruplexes; D008969:Molecular Sequence Data; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052156:SELEX Aptamer Technique
chemical_list: D052157:Aptamers, Nucleotide; C558493:HJ24 aptamer; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11