Tyrosine-specific kinase

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Based on their substrate specificity, kinases have been divided into two broad classes serine/threonine- and tyrosine-specific kinases. Of the estimated 500 kinases, roughly one-fifth of these are tyrosine kinases. The two classes are further broken down and grouped by function, required cofactors, and substrates. ... 

Protein kinases can be classified according to the amino acid residue that is phosphorylated in the cellular process. Consequently, there are tyrosine-specific kinases and serine/threonine kinases. Tyrosine kinases are a family of tightly regulated enzymes, and the aberrant activation of various members of this family is one of the hallmarks of cancer. Tyrosine phosphorylation has been linked to multiple cell growth and differentiation pathways. Imatinib mesylate (1) is a tyrosine kinase inhibitor (TKI). An important characteristic of imatinib mesylate (1) is that it is an ATP-competitive inhibitor. It binds at the ATP binding site and blocks ATP binding thereby inhibiting kinase activities. 

Reddy, E.P. Smith, M.J. Srinivasan, A. Nucleotide sequence of Abelson murine leukemia virus genome structural similarity of its transforming gene product to other one gene products with tyrosine-specific kinase activity. Proc. Natl. Acad. Sci. USA, 80, 3623-3627 (1983)... 

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