Homo-tyrosine

A second example of this methodology comes from the Merck synthesis of homo-tyrosine, an intermediate for a potent do >amine agonist (Scheme 27). The Grignard reagent is added to a solution of 2 equiv. of diethyl oxalate at -20 C. 

ErbB (or HER in the human). There are four ErbB receptors that form homo- or heterodimers in various combinations upon ligand binding. Specific NRG isoforms preferentially interact with different ErbB dimers. The ErbB receptors are ligand-activated tyrosine kinases structurally similar to the EGF receptor. 

Lenferink, A. E., R. Pinkas Kramarski, M. L. van de Poll, M. J. van Vugt, L. N. Klapper, E. Tzahar, H. Waterman, M. Sela, E. J. van Zoelen, and Y. Yarden. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 17 3385-3397.1998. 

Solutes 1 = homo-vanillic acid, 2 = 5-hydroxyindol-3-acetic acid, 3 = 3,4-dihydroxyphenylacetic acid, 4 = tyrosine, 5 - L-DOPA, 6 = dopamine, 7 = octopamine, 8 = adrenaline, 9 = 3,4-dihydroxymandelic acid, 10 = noradrenaline. 

Cephalotaxus Alkaloids.—Preliminary results indicate that the homo-Erythrina alkaloid schelhammeridine (52) derives from phenylalanine and tyrosine by way of a phenethylisoquinoline precursor [as (53)].52 Previous evidence for the biosynthesis of the related alkaloid cephalotaxine (54), obtained with tyrosine labelled in the side-chain, has indicated a different pathway which involves two molecules of this amino-acid.53 Recently, however, tyrosine labelled in the aromatic ring was examined as a cephalotaxine precursor and was found54 to label ring A of (54) almost exclusively, i.e. only one unit of tyrosine is used for biosynthesis. This is obviously inconsistent with the previous evidence and the early incorporations are... 

Acidic and basic fibroblast growth factors (FGFs) Tissue-specific functions FGFs bind to heparan-sulphate glycosaminoglycans FGFRs Homo and heterodimeric tyrosine kinases... 

The insulin receptor is the prototype of a tyrosine kinase receptor with a constitutive oligomeric structure. The signalling form is a a.2/ 2 tetramer, but the unit structure is a heterodimer, consisting of a- and P-subunits. But, in contrast to the homo-and heterodimers of other RTK growth factor receptors, the formation of the insulin receptor oligomer is constitutive and not dependent on ligand binding (see Fig. 1.5). 

RET is a human protoonco ne which encodes the RET receptor. There are two forms of receptors with tyrosinekinase activity. They are orphan receptors with unknown ligands. Oncogenic variants are found which are constitutively phosphorylated on tyrosines and form homo-and heterodimers. These variants have been found in endocrine disorders, MEN, and in Hirschsprung s disease. 

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