Phenylalanine analogs

Like the glucose carrier, the carriers for large neutral amino acids, the so-called L-system - now designated LAT - are present at both sides of the endothelial cell membranes and transport at least 10 essential amino acids. The L-transporter at the BBB has a much higher transport capacity than those in other tissues. Its marked preference for phenylalanine analogs explains why the anticancer drugs melphalan and d,l-NAM-7 are transported by the L-system, as is the L-Dopa used to treat Parkinson s disease [42]. 

W. Liu, Synthesis of Optically Active Phenylalanine Analogs using Rhodotorula grami-nis, Great Lakes Chemical Corp., 1997, US 5981239. 

Gibson et al. [152], in their bromoarene-based approach to phenylalanine analogs, describe a 9-e preparative reaction scale (Scheme 6.65). 

Fig. 9. Structures of phenylalanine (1 ) and of phenylalanine analogs discussed in the text. ( ), 5-(l-amino-2-phenylethyl)tetrazole ( ), (1-amino-2-phenylethy1) phosphonic acid ( ), (l-amino-2-phenylethyl)phosphonous acid ( ), a-aminooxy-8-phenylpropionic acid ( ), a-hydrazino-6-phenylpropionic acid (7 ), 3-methylene-phenylalanine (S), (1,4-cyclohexadienyl)-alanine ( ), o-carboranylalanine (10), adamantylalanine.

The inhibition of amino acid incorporation in suspensions of the EhrHch ascites carcinoma has been studied by Rabinovitz et Both o-fluorophenylalanine and 8-2-thienylalanine were found to be competitive antagonists against phenylalanine, with o-fluorophenylalanine being five times as potent. The two amino acid analogs and phenylalanine itself inhibited the initial rate of incorporation of radioactive valine, leucine, and lysine competitively and in an almost identical manner. This indicates that the inhibition of the incorporation of the other amino acids by the phenylalanine analogs is not related to the latter s effect upon phenylalanine incorporation but is an independent inhibition of the incorporation of each amino acid. 

An aromahc L-amino acid transaminase from Enterobacter sp. with unknown structure and no substrate specificity toward aromahc amino acid analogs was used to synthesize the L-phenylalanine analog L-diphenylalanine. Based on the interaction of fhe substrafe wifh the achve site of fhe enzyme, sife-directed mutagenesis can alter the substrate specificity of the transaminase toward substrates with bulky side chains [118]. 

It is worth noting here that Hoffman et al. (184) recently found that a phenylalanine analog of ACTH was devoid of enzymatic activity, but exhibited affinity for the ACTH receptor. For these reasons. Coy et al. (90) suggested that the essential feature of tryptophan in maintaining hormonal action was due to its electron-donating properties. 

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