Development of activity-based probes with tunable specificity for protein tyrosine phosphatase subfamilies

TETRAHEDRON

卷:66

Article

Huang, Yu-Yen²  Kuo, Chun-Chen³  Chu, Chi-Yuan²  Huang, Yung-Hsuan²  Hu, Yi-Ling²  Lin, Jing-Jer^1,3  Lo, Lee-Chiang² 

[1] Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan

[2] Natl Taiwan Univ, Dept Chem, Taipei 106, Taiwan

[3] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan

关键词: Activity-based;    Enzymes;    Tyrosine phosphatase;    Quinone methide;    Peptides;    Biotin;   

DOI  :  10.1016/j.tet.2010.04.065

来源: Elsevier

【 摘 要 】

Herein we describe the development of activity-based probes toward protein tyrosine phosphatase (PTP) subfamilies. A novel phosphotyrosine analog serving as the latent trapping unit has been designed and explored. It allows addition of various amino acid residues to its C- and N-termini to extend the recognition element. As a proof-of-concept, we have synthesized three tripeptide probes, which carry the phosphotyrosine analog in the middle position and a leucinamide residue at the C-terminus. The three tripeptide probes differed only in their N-terminal amino acid (Glu, Phe, and Lys). The labeling properties of these probes were determined and the results showed the newly synthesized probes could selectively label PTPs in an activity-dependent manner. In addition, the probes' target specificity was also shown to be influenced by the amino acid residues flanking the phosphotyrosine analog. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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