Amino acids A/-methylation

The D (R) isomer of the amino acid A-methyl aspartate, more familiarly known as NMDA, serves as the endogenous agonist at a number of central nervous system (CNS) receptor sites. This agent is not only involved in neurotransmission, but it also modulates responses elicited by other neurochemicals. 

The D(R) isomer of the amino acid A-methyl-D-aspartate, more commonly known as NMDA serves as the endogenous agonist at a number of central nervous system (CNS) receptor sites. This agent is not only involved in neurotransmission, but also modulates responses elicited by other neurochemicals. A relatively simple peptide-like molecule has been found to act as an antagonist at NMDA receptors. This activity is manifested in vivo as antiepdeptic activity. This agent in addition blocks the nerve pain suffered by many diabetics, which is often called neuropathic pain. The synthesis begins by protecting the unnatural D-serine... 

Figure 39.1a shows the generic structure of microcystins (MC), with the two most variable positions marked by X and Z. The numbering of the individual positions was done before the elucidation of the biosynthetical pathway and is arbitrary (see below). MCs are cyclic heptapeptides with several structural peculiarities. The moiety characteristic of microcystins and nodularins is the Adda, abbreviated for 3-amino-9-methoxy-2,6,8,-trimethyl-10-phenyl-4,6-decadienoic acid, a P-amino acid that is not known from other natural products. Further peculiarities of the molecule are o-amino acids. These stereoisomers of commonly occurring L-amino acids are not found in ribosomally synthesized proteins and peptides and are therefore called nonproteinogenic amino acids. A-methyl-dehydroalanine (Mdha) in position 7 also is a nonproteinogenic amino acid as it is the case with o-erythro-P-methyl-iso-aspartate (o-MeAsp). 

Chiral a-amino acids, a-methyl amino acids and ahphatic or aromatic a-hydroxycarboxylic acids, chiral iV-alkyl, iV-carbamyl, and iV-formyl amino acids, dipeptides and heterocyclic compounds... 

A similar series of conversions occurs after the administration of the related amino acid, a-methyl-me/a-tyrosine. leading in this case to the production of L-metaraminol. In some species a microsomal hydroxylating system can also catalyse the introduction of a phenolic hydroxyl group into L-metaraminol or one of its precursors, so that the final product stored in the adrenergic nerves may be a mixture of metaraminol and oc-methylNA (Fig. 10). Again the amount of... 

RS- P-Aminoisobutyric acid (a-methyl-P-alanine) [10569-72-9] M 103.1, m 176-178 , 178-180 , 181-182 , R -(-)- isomer [144-90-1] m 183 , [a] -21 (c 0.43, HjO), pKes,(,) 3.7, pKEst(2) 10.2. Colorless prisms from hot H O, were powdered and dried in vacuo. The purity is checked by paper chromatography (Whatman 1) using ninhydrin spray to visualise the amino acid Rp values in 95% MeOH and n-PrOH/5N HCOOH (8 2) are 0.36 and 0.50 respectively. [Kupiecki and Coon Biochem Prep 7 20 7960 Pollack J Am Chem Soc 65 1335 7943.] The R-enantiomer, isolated from iris bulbs or human urine was crystd from H2O and sublimed in vacuo [Asen et al. J Biol Chem 234 343 7959]. The RS-hydrochloride was recrystd from EtOH/Et20 m 128-129 , 130° [Bbhme et al. Chem Ber92 1258, 1260, 1261 7959]. 

N-derivatized a-amino acids N-methyl tert-butyl carbamoylated quinine Methanol—O.IM 203 ammonium acetate, pH 6.0 (80 20)... 

Unnatural amino acids are added to the growth medium in most experiments. There are a large number of amino acid and amine transporters that are relatively nonspecific and which may help to transport the unnatural amino acids into cells. From measurements of cytoplasmic levels of amino acids, it is found that a large number of unnatural amino acids are efficiently transported to the E. coli cytoplasm in millimolar concentrations. Highly charged or hydrophilic amino acids may require derivatization (e.g., esterification, acylation) with groups that are hydrolyzed in the cytoplasm. Metabolically labile amino acids or analogues (e.g., a-hydroxy acids, A-methyl amino acids) may require strains in which specific metabolic enzymes are deleted. 

The main genera responsible for freshwater toxic blooms are Microcystis, Anabaena, Aphanizomenon and Oscillatoria. Toxins produced include 1. anatoxins, alkaloids and peptides of Anabaena 2. the peptide microcystin and related peptides of Microcystis 3. aphantoxins, compounds of Aphanizomenon with properties similar to some paralytic shellfish poisons. Properties of Oscillatoria toxin suggest they are peptides similar to those of Microcystis. Microcystis toxins are peptides (M.W. approx. 1200) which contain three invariant D-amino acids, alanine, erythro-3-methyl aspartic and glutamic acids, two variant L-amino acids, N-methyl dehydro alanine and a 3-amino acid. Individual toxic strains have one or more multiples of this peptide toxin. The one anatoxin characterized is a bicylic secondary amine called anatoxin-a (M.W. 165). The aphantoxin isolated in our laboratory contains two main toxic fractions. On TLC and HPLC the fractions have the same characteristics as saxitoxin and neosaxitoxin. 

The cosmopolitan cyanobacterium Microcystis aeruginosa is frequently the major component of freshwater cyanobacterial blooms. These blooms can cause serious water management problems and are occasionally associated with animal poisoning. The aeruginosa toxins are potent lethal peptides which contain three invariant D-amino acids (Ala, erythro-3-methyl Asp, and Glu), two variant L-amino acids, N-methyl dehydroalanine, and a 3 amino acid (1-3). Multiple toxins have been purified from clonal isolates (1,4). The toxic peptide described in this chapter is denoted toxin-LR using the standard one-letter abbreviations for its two variant amino acids, leucine and arginine. 

L-Alanine, the simplest chiral amino acid, has been the subject of the most extensive study and serves as the prototype for the other amino acids. A complete vibrational assigrunent has been obtained (85, 86) based on solution phase IR and Raman spectra and solid phase Raman spectra for alanine-do, alanine-C -di, alanine-C(3-d3, and alanine-C -d-C -d3. In the CH stretching region, the antisymmetric methyl stretches are assigned at 3006 and 2989 cm , the methine stretch at 2970 cm , and the Fermi resonance diad involving the symmetric methyl stretch and the overtone of the antisymmetric methyl deformation at 2950 and 2893 cm. The calculated frequency for the unperturbed symmetric methyl stretch is 2930 cm . 

The use of mixed anhydrides derived from Al-acyl-a-amino acids has become an interesting strategy for synthesis of saturated 5(4//)-oxazolones 101 (Scheme 7.26). For example, reaction of Al-acyl-a-amino acids with methyl chloroformate in the presence of Al-methylmorpholine affords racemic 5(47/)-oxazolones. 

Bisebromoamide is cytotoxic linear peptide isolated from the marine cyanobacterium Lyngbya sp. (Teruya et al., 2009). Structure of bisebromoamide contains rich unusual amino acid derivatives with D-amino acids, N-methylated amino acids, a brominated tyrosine, a modified 4-methylpro-line, a 2-substituted thiazoline-4-methyl-4-carboxylic acid unit, and a rare... 

Conjugation involves addition of an endogenous moiety to a foreign molecule, which may be a product of a phase 1 reaction. Major phase 2 routes conjugation with glucuronic acid, sulfate, glutathione amino acids acetylation methylation. Enzymes involved are transferases except in the case of amino acid conjugation where the first step is catalyzed by an acyl CoA synthetase, then a transferase is involved. 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

Arenediazonium tetrafluoroborates, 19 Azidotrimethylsilane, 24 N-Chlorosuccinimide, 79 Diphenyldiazomethane, 242 a-Substituted a-amino acids a-Methylbenzylamine, 185 Methyl N-benzyloxy carbonyl-a-chloro-glycinate, 186 Pivaldehyde, 249 Miscellaneous compounds Diisobutylaluminum hydride-Boron trifluoride etherate, 116 Tin(IV) chloride, 300 Amino alcohols... 

The formation of methyl (S)-thiiranecarboxylate (5) is of interest,3 since in this case the leaving group is a diazo residue originating from an amino group. The starting material is therefore the chiral amino acid ester, methyl (R)-cystein-ate, and the stereoelectronic requirements of the reaction lead to an optically pure product of predictable stereoisomeric form (Expt 8.2). 

C21. Crumpler, H. R., Dent, C. E., Harris, H., and Westall, R. G., P-aminoiso-butyric acid (a-methyl-p-alanine) a new amino-acid obtained from human urine. Nature 167, 307-308 (1951). 

Chemical Name Benzeneacetic acid, a-methyl-4-((2-methyl-2-propenyl) amino)-... 

Based on experience, the following procedure was suggested for the preparation of TFA-amyl esters of amino acids. A sample of amino acids (0.5—2 mg of each acid) was placed into a test-tube and dissolved in 0.2 ml of trifluoroacetic acid. Amyl alcohol (2 ml) was added and dry hydrogen chloride was bubbled through the reaction mixture continuously at 108°C for 25 min. Excess of the reagent was removed under vacuum, dissolved in a small amount of methanol, transferred into a small test-tube and the methanol was evaporated by standing freely at 70°C. TFA anhydride (1 ml) was added and the stoppered test-tube was allowed to stand at room temperature for 1 h. As some of the amino acids (e.g., Arg) were not acylated quantitatively by this procedure, it was recommended that the sealed test-tube be heated at 140°C for 5 min [229]. Excess of anhydride was removed under vacuum and the residue was dissolved in a known volume of dry methyl ethyl ketone. 

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