Specific monitoring of Syk protein kinase activity by peptide substrates including constrained analogs of tyrosine

FEBS Letters

Cesaro, Luca¹  Ruzza, Paolo²  Brunati, Anna Maria¹  Borin, Gianfranco²  Pinna, Lorenzo A¹  Calderan, Andrea²  Donella-Deana, Arianna¹ 

[1] Dipartimento di Chimica Biologica and Centro di Studio delle Biomembrane del CNR, University of Padova, Viale G. Colombo 3, 35121 Padua, Italy;CNR-Istituto di Chimica Biomolecolare, Sezione di Padova, Padua, Italy

关键词: Protein kinase;    Syk tyrosine kinase;    Peptide;    Tyrosine analog;    Peptide phosphorylation;    PTK;    protein tyrosine kinase;    HBTU;    2-(1H-benzotriazol-1-yl)-1;    1;    3;    3-tetramethyl uronium hexafluorophosphate;   

DOI  :  10.1016/S0014-5793(02)02932-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ability of Syk protein tyrosine kinase (PTK) to phosphorylate peptides, where tyrosine had been replaced by conformationally constrained analogs, has been exploited to develop highly selective substrates suitable for the specific monitoring of Syk activity. In particular we have synthesized a peptidomimetic, RRRAAEDDE(L-Htc)EEV (syktide), with the 3(S)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxyl acid residue (L-Htc) replaced for tyrosine, which is phosphorylated by Syk with remarkable efficiency (K _cat=73 min⁻¹, K _m=11 μM), while it is not affected to any appreciable extent by a number of PTKs tested so far. These properties make syktide the first choice substrate for the specific monitoring of Syk.

【 授权许可】

Unknown