Design and synthesis of class-selective activity probes for protein tyrosine phosphatases

• Published in: Journal of proteome research Vol. 1; no. 1; p. 35
• Main Authors: Lo, Lee-Chiang, Pang, Te-Ling, Kuo, Chi-Hsien, Chiang, Ying-Ling, Wang, Hsin-Yi, Lin, Jing-Jer
• Format: Journal Article
• Language: English
• Published: United States 01.01.2002
• Subjects: Enzyme Activation; Molecular Probes - chemical synthesis; Molecular Probes - chemistry; Molecular Structure; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - metabolism; Sensitivity and Specificity; Substrate Specificity
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/pr015506a

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.