Abstract：
:Although peptide-based reporters of protein tyrosine kinase (PTK) activity have been used to study PTK enzymology in vitro, the application of these reporters to intracellular conditions is compromised by their dephosphorylation, preventing PTK activity measurements. Nonproteinogenic amino acids may be utilized to rationally design selective peptidic ligands by accessing greater chemical and structural diversity than is available using the native amino acids. We describe a peptidic reporter that, upon phosphorylation by the epidermal growth factor receptor (EGFR), is resistant to dephosphorylation both in vitro and in cellulo. The reporter contains a conformationally constrained phosphorylatable moiety (7-(S)-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) in the place of L-tyrosine and is efficiently phosphorylated in A431 epidermoid carcinoma cells. Dephosphorylation of the reporter occurs 3 orders of magnitude more slowly compared with that of the conventional tyrosine-containing reporter.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Turner AH,Lebhar MS,Proctor A,Wang Q,Lawrence DS,Allbritton NLdoi
10.1021/acschembio.5b00667subject
Has Abstractpub_date
2016-02-19 00:00:00pages
355-62issue
2eissn
1554-8929issn
1554-8937journal_volume
11pub_type
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