Methyltyrosine

CF3SO3H, PhSMe, 0-25°. ° In this case O-methyltyrosine was depro-tected without evidence for O C migration, which is often a problem when removing protective groups from tyrosine. 

N-methyltyrosine ((3-p-hydroxyphenyl-a-methylaminopropionic acid) under the names angeline, andirine, geoffroyine, surinamine and rhatanine has been isolated from Ferreira sj ciabilis, Audit a retusa, A. inermis, Geqffroea sumamensis and Krameria triandra. ... 

Fluororesorcinol can be prepared from derivatives of resorcinol and fluo-roxytrifluoromethane [15, 24] (equation 4) or by fluorination of resorcinol with cesium fluoroxysulfate [25] (equation 5). Reaction of acetyl hypofluorite with M-acetyl-O-methyltyrosine methyl ester provides a good route to 3-fluorotyrosine derivatives [26] (equation 6). 

QUESTION Do you get bigger effects on some of the behavioral parameters after the amphetamine treatments if you pretreat the animals with a low dose of alpha methyltyrosine during that period, during the postamphetamine period In the old days, when we had a partial lesion, we gave a low dose of AMFT, and it would reexpose the lesion. Have you tried that ... 

Commins, D.L., and Seiden, L.S. Alpha-methyltyrosine blocks methylamphetamine-induced degeneration in the rat somatosensory cortex. Brain Res 365 15-20, 1986. 

QUESTION How do you imagine that both a receptor antagonist and an uptake inhibitor would block the effects It would seem that if dopamine is involved, it would either be acting on a membrane receptor or inside, but not both. I would also like to ask a more specific question. You showed that the alpha MT protected effect could be reversed by dopa. And I think you imagined that that was because of dopamine formation. But have you tried dopamine agonists to see if they would antagonize either the protective effect of alpha methyltyrosine or, particularly, the protective effect of the dopamine antagonists to try to verily that those protective effects really have to do with blockade of a dopamine receptor as opposed to some other possibility ... 

In testing the possibility of proton transfer as a quenching mechanism of tyrosine in oligopeptide/polynucleotide complexes, Brun et a/.(102) compared the fluorescence emission spectra of the tyrosine and O-methyltyrosine tripeptides. They noted that, in the complex, the O-methyltyrosine tripeptide had a unique secondary emission near 410 nm. Whether this emission is related to that observed by Libertini and Small(94) is an important question. While one must consider the possibility that two tyrosine side chains could be converted to dityrosine, (96) which has a fluorescence at 400 nm, another intriguing possibility is ambient temperature tyrosine phosphorescence. This could happen if the tyrosine side chain is in a rigid, protective environment, very effectively shielded from collisions with quenchers, particularly oxygen. 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

Metyrosine Metyrosine, (-)a-methyltyrosine (12.3.11), is synthesized in a few different ways, the simplest of which is the synthesis from 4-methoxybenzylacetone, which is reacted with potassium cyanide in the presence of ammonium carbonate to give the hydan-toin (12.3.9). Treating this with hydrogen iodide removes the methyl-protecting group on the phenyl hydroxyl group and the product (12.3.10) is hydrolyzed by barium hydroxide into a racemic mixture of a-methyl-D,L-tyrosine, from which the desired L-isomer is isolated (12.3.11) [83-86]. 

Dopamine synthesis inhibitors interfere with the enzymes involved, and are identical to those discussed in section 4.3.5 (e.g., a-methyltyrosine (4.74), a tyrosine hydroxylase inhibitor). In this case, aj-adrenergic receptor effects are irrelevant, and only the classical competitive inhibitory effect is of any consequence. 

Biosynthesis of catecholamines. The rate-limiting step, conversion of tyrosine to dopa, can be inhibited by metyrosine (K-methyltyrosine). The alternative pathway shown by the dashed arrows has not been found to be of physiologic significance in humans. However, tyramine and octopamine may accumulate in patients treated with monoamine oxidase inhibitors. 

Pheochromocytoma is sometimes treated with metyrosine (cx-methyltyrosine), the -methyl analog of tyrosine. This agent is a competitive inhibitor of tyrosine hydroxylase, the rate-limiting step in the synthesis of dopamine, norepinephrine, and epinephrine (see Figure 6-5). Metyrosine is especially useful in symptomatic patients with inoperable or metastatic pheochromocytoma. Because it has access to the central nervous system, metyrosine can cause extrapyramidal effects due to reduced dopamine levels. 

Pseudomonas and rat liver phenylalanine 4-Methylphenyl- alanine m-Methyltyrosine — 102... 

The prevalent Microcystis aeruginosa has afforded the plasmin inhibitors micropeptins 478-A (1115) and 478-B (1116) (1133). The terrestrial cyanobacterium Scytonema hofmanni PCC 7110 gives rise to scyptolins A (1117) and B (1118), which contain the 3-chloro-A-methyltyrosine residue (1134). The binding of 1117 to pancreatic elastase has been determined by X-ray crystallography (1135). Myriastramide B (1119) was isolated from the Philippine sponge Myriastra clavosa and features a novel chlorinated ether moiety (1136). 

Tyrosine is converted to dopa by the rate-limiting enzyme tyrosine hydroxylase, which requires tetrahydrobiopterin, and is inhibited by a-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which requires pyridoxal phosphate (vitamin B6) as a coenzyme. Carbidopa, which is used with levodopa in the treatment of parkinsonism, inhibits this enzyme. Dopamine is converted to norepinephrine by dopamine P-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenylethanolamine A -methyltransferase (PNMT), requiring S-adeno-sylmethionine. The activity of PNMT is stimulated by corticosteroids. 

In a second method rabbit antibodies were produced against a butanoic acid derivative of pentazocine which was conjugated to bovine serum albumin via a carbodiimide condensation. An 25i labeled methyltyrosine pentazocine giving 25.000-... 

Chemical Name 0-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-a-methyltyrosine ethyl ester... 

FIGURE 12. Clonogenic survival of B16 melanoma cells exposed to 211At-labelled a-methyltyrosine for 45-min incubation period. 1 pCi = 37 Bq. Reproduced by permission of Academic Press from Reference 123... 

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