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An Exploration of the Effects of Constraints on the Phosphorylation of Synthetic Protein Tyrosine Kinase Peptide Substrates
Author(s) -
Ruzza Paolo,
DonellaDeana Arianna,
Calderan Andrea,
Filippi Bruno,
Cesaro Luca,
Pinna Lorenzo A.,
Borin Gianfranco
Publication year - 1996
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.70
Subject(s) - autophosphorylation , phosphorylation , peptide , moiety , chemistry , stereochemistry , tyrosine , lyn , kinase , proto oncogene tyrosine protein kinase src , tyrosine kinase , biochemistry , sequence (biology) , combinatorial chemistry , protein kinase a , signal transduction
We synthesized by classical solution methods three conformational constrained analogues of EDNEYTA, a heptapeptide sequence that represents the common major autophosphorylation site of the protein tyrosine kinases (PTKs) of the Src family. The correlation between the different structural properties induced by the modifications of the native sequence and the propensity of the peptides to act as PTK substrates was examined. The kinetic data obtained indicate that the introduction of the tyrosine‐analogue constraints Tic(OH) and MeTyr, which block the ring flexibility, completely prevents the phosphorylation catalysed by the kinases Lyn and Fgr. On the other hand PTKIIB/p38 syk can phosphorylate the two derivatives albeit with an efficiency lower than that found with the native sequence. A third derivative contained side chain to side chain cyclization. This analogue, in which the freedom of the phenolic moiety is not altered, can be phosphorylated by all the PTKs tested with kinetic constants comparable to the parent peptide.