Design and synthesis of class-selective activity probes for protein tyrosine phosphatases.
Two mechanism-based activity probes, adopting a cassette-like design, for protein tyrosine phosphatases (PTPs) were synthesized. Both probes carry a phosphate group that serves as the recognition head for the target PTPs but differ in their reporter groups; probe LCL-1 uses a dansyl fluorophore, while LCL-2 has a biotin reporter group. LCL-1 and LCL-2 are specifically activated by phosphatase, leading to its covalent labeling, as exemplified with PTP-1B. However, they show no activation with other classes of hydrolases, including trypsin and beta-galactosidase. LCL-1 and LCL-2 thus represent the first example of class-selective probes for phosphatases.
Lo
Lee-Chiang
LC
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan. lclo@ccms.ntu.edu.tw
Pang
Te-Ling
TL
Kuo
Chi-Hsien
CH
Chiang
Ying-Ling
YL
Wang
Hsin-Yi
HY
Lin
Jing-Jer
JJ
D004789:Enzyme Activation; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013379:Substrate Specificity
D015335:Molecular Probes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases