Document Detail

Spatial conformation and topography of the tyrosine aromatic ring in substrate recognition by protein tyrosine kinases.
MedLine Citation:
PMID:  16539378     Owner:  NLM     Status:  MEDLINE    
The side chain orientation of the tyrosine residue included in a peptide, which is an excellent substrate of Syk tyrosine kinase, was fixed in different conformations by either incorporating the tyrosine in cyclic structures (6-OH-Tic, 5-OH-Aic, and Hat derivatives) or adding a sterically bulky substituent in the tyrosine side chain moiety (beta-MeTyr). Synthetic peptides containing tyrosine analogues displaying different side chain orientations were analyzed by NMR techniques and tested as potential substrates of the nonreceptor tyrosine kinases Syk, Csk, Lyn, and Fyn. The "rotamer scan" of the phosphorylatable residue generated optimal substrates in terms of both phosphorylation efficiency and selectivity for Syk tyrosine kinase, while the peptidomimetics were not recognized by the other tyrosine kinases. In particular, l-beta-MeTyr and d-Hat containing peptides resulted to be both suitable substrates for the specific monitoring of Syk and consensus sequence scaffolds for the design of potential inhibitors highly selective for this tyrosine kinase.
Paolo Ruzza; Luca Cesaro; Dirk Tourwé; Andrea Calderan; Barbara Biondi; Veronique Maes; Ileana Menegazzo; Alessio Osler; Chiara Rubini; Andrea Guiotto; Lorenzo A Pinna; Gianfranco Borin; Arianna Donella-Deana
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  49     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-16     Completed Date:  2006-04-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1916-24     Citation Subset:  IM    
Institute of Biomolecular Chemistry of CNR, Padova Unit, via F. Marzolo 1, 35131 Padova, Italy.
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MeSH Terms
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Molecular Mimicry
Oligopeptides / chemical synthesis,  chemistry*
Protein-Tyrosine Kinases / antagonists & inhibitors,  chemistry*
Structure-Activity Relationship
Substrate Specificity
Tyrosine / chemistry*
Reg. No./Substance:
0/Oligopeptides; 55520-40-6/Tyrosine; EC Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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