- Mechanism of Buffer Catalysis in the Iodine Oxidation of N-Acetylmethionine Methyl Ester
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The iodine oxidation of N-acetylmethionine methyl ester is catalyzed by carboxylic acid buffers.At very low concentrations, the reaction is first order with respect to buffer and follows an iodide dependence that can be described as inverse squared, changing to invers cubed as the iodide concentration is increased.This iodide dependence is observed at all buffer concentrations examined, although the transition from inverse squared to inverse cubed occurs at higher iodide concentrations as the buffer concentration is increasd.As the buffer concentration is increased, the observed rate constants become dependent upon 2 and at "high" buffer (typically > 0.3 M) the reaction again becomes first order with respect to buffer.Broensted coefficients, based on four carboxylic acid buffers, are 1.0 and 1.5 for the first- and second-order terms, respectively.In the reaction catalyzed by acetate, acetic anhydride is produced in an amount equal to the concentraion of sulfide that is oxidized.The data are rationalized in terms of a mechanism involving the rapid formation of an iodosulfonium ion which is attacked by buffer to give an intermadiate O-acylsulfoxide.The O-acylsulfoxide can partition by back-reaction with iodide or by attack of buffer or water at the acyl carbon to give either unhydride or free acid.The βeq for O-acylsulfoxide formation is estimated to be 1.5.Possible transition states for O-acylsulfoxides formation and the possible roles of sulfurane intermediates in these reactions are discussed.
- Young, Paul R.,Hsieh, Li-Shan
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- Looking glass mechanism-based inhibition of peptidylglycine α-amidating monooxygenase
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Carboxyl-terminal amidation, a required post-translational modification for the bioactivation of many peptide hormones, entails sequential enzymatic action by peptidylglycine α-monooxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5). We have previously demonstrated that PAM and PGL exhibit strict tandem reaction stereospecificities, with PAM producing exclusively α-hydroxyglycine moieties of absolute configuration (S), and PGL being reactive only toward (S)-α-hydroxyglycines, and we have also shown that PAM exhibits strict P2-subsite stereospecificity toward both peptide substrates and peptidyl competitive inhibitors. Herein, it is reported that the inhibitory stereochemistry of olefinic mechanism-based amidation inhibitors differs from the strict subsite stereospecificity exhibited by PAM toward substrates and reversible competitive inhibitors. Kinetic analyses of mechanism-based irreversible inhibition of PAM by the (S)- and (R)-enantiomers of 5-acetamido-4-oxo-6-phenyl-2-hexenoic acid were carried out using the rigorous progress curve method. The two enantiomers were found to exhibit very similar values of KI and kinact and in both cases kinetic analysis confirmed that irreversible inhibition occurs strictly at the substrate binding site with no ESI complex being formed during the catalytic processing of these irreversible inhibitors. Molecular docking studies were carried out to help rationalize the sharp contrast in the stereospecificity of PAM toward irreversible inhibitors versus substrates and competitive inhibitors. The results revealed that, in contrast to substrates, both docked enantiomers of the olefinic irreversible inhibitors are well-positioned to undergo catalytic processing at the Cu center that gives rise to irreversible inhibition. Taken together, these results provide one of the first clear examples where the stereospecificity of a particular enzyme toward mechanism-based irreversible inhibitors differs from that for substrates and competitive inhibitors.
- Foster, Michael S.,Oldham, Charlie D.,May, Sheldon W.
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experimental part
p. 283 - 293
(2011/05/17)
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- Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid δ13C values for palaeodietary and palaeoecological reconstruction
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Results are presented of a comparison of the amino acid (AA) δ13C values obtained by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) and liquid chromatography-isotope ratio mass spectrometry (LC/IRMS). Although the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA δ13C values are required. We compare LC/IRMS with the most up-to-date GC/C/IRMS method using N-acetyl methyl ester (NACME) AA derivatives. This comparison involves the analysis of standard AAs and hydrolysates of archaeological human bone collagen, which have been previously investigated as N-trifluoroacetyl isopropyl esters (TFA/IP). It was observed that, although GC/C/IRMS analyses required less sample, LC/IRMS permitted the analysis of a wider range of AAs, particularly those not amenable to GC analysis (e.g. arginine). Accordingly, reconstructed bulk δ13C values based on LC/IRMS-derived δ13C values were closer to the EA/IRMS-derived δ13C values than those based on GC/C/IRMS values. The analytical errors for LC/IRMS AA δ13C values were lower than GC/C/IRMS determinations. Inconsistencies in the δ13C values of the TFA/IP derivatives compared with the NACME- and LC/IRMS-derived δ13C values suggest inherent problems with the use of TFA/IP derivatives, resulting from: (i) inefficient sample combustion, and/or (ii) differences in the intra-molecular distribution of δ13C values between AAs, which are manifested by incomplete combustion. Close similarities between the NACME AA δ13C values and the LC/IRMS-derived δ13C values suggest that the TFA/IP derivatives should be abandoned for the natural abundance determinations of AA δ13C values.
- Dunn, Philip J. H.,Honch, Noah V.,Evershed, Richard P.
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p. 2995 - 3011
(2012/05/20)
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- Alternative and chemoselective deprotection of the α-amino and carboxy functions of N-Fmoc-amino acid and N-Fmoc-dipeptide methyl esters by modulation of the molar ratio in the AlCl3/N,N-dimethylaniline reagent system
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The amino and carboxy functions in N-Fmoc-α-amino acid and N-Fmoc-peptide methyl esters can be alternatively and chemoselectively deprotected by treatment with the reagent system AlCl3/N,N- dimethylaniline (DMA). The chemoselectivity of the process is controlled by modulating the relative molar ratio of the Lewis acid and DMA. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Di Gioia, Maria Luisa,Leggio, Antonella,Le Pera, Adolfo,Liguori, Angelo,Perri, Francesca,Siciliano, Carlo
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p. 4437 - 4441
(2007/10/03)
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- Chloroperoxidase-catalyzed oxidation of methionine derivatives
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Treatment of N-methoxycarbonyl C-carboxylate ester derivatives of L- and D-methionine and L-ethionine by chloroperoxidase-hydrogen peroxide resulted in oxidation at sulfur to produce the (RS) sulfoxide in moderate to high diastereomeric excess.
- Holland, Herbert L.,Brown, Frances M.,Lozada, Damian,Mayne, Benjamin,Szerminski, W. Rick,Van Vliet, Aaron J.
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p. 633 - 639
(2007/10/03)
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- Use of enantio-, chemo- and regioselectivity of acylase I. Resolution of polycarboxylic acid esters
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Acylase I was used to catalyze the enantioselective butanolysis of trimethyl 2-[(carboxymethyl)oxy]succinate (E=30) and N-carboxymethylaspartate (E=9) exclusively at the most sterically hindered of the three ester groups (the position α to the asymmetric centre). Gram-scale resolution allowed the preparation of the less reactive trimethyl (S)-2-[(carboxymethyl)oxy]succinate (96% e.e.), that of the (R)-butyldimethyl regioisomer (78% e.e.) at 55% conversion and finally the preparation of the corresponding trisodium carboxylate by saponification. Acylase I was shown to transform (±)-methyl N-acetylmethionine and (±)-valine to the corresponding (S)-amino acids through ester hydrolysis-N-acetyl transfer sequence with absolute chemo- and enantioselectivity. Butanolysis of methyl N-acetylmethionine stopped in the formation of the butyl ester (E=12), the valine derivative being totally unreactive.
- Liljeblad, Arto,Aksela, Reijo,Kanerva, Liisa T.
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p. 2059 - 2066
(2007/10/03)
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- SYNTHESIS OF FLUORINATED DERIVATIVES OF METHIONINE AND 5'-DEOXY-5'-(METHYLTHIO)-ADENOSINE USING THE McCARTHY TRANSFORMATION OF SULFOXIDES TO α-FLUORO THIOETHERS
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Treatment of N-acetylmethionine sulfoxide methyl ester with diethylaminosulfur trifluoride (DAST) or dimethylaminosulfur trifluoride (meDAST) yielded N-acetyl-S-(monofluoromethyl)homocysteine methyl ester as the sole fluorinated product.In contrast, treatment of 2',3'-di-O-acetyl-5'-(methylthio)adenosine sulfoxide with DAST or meDAST unexpectedly produced three novel fluorinated products.
- Sufrin, Janice R.,Spiess, Arthur J.,Alks, Vitauts
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p. 177 - 182
(2007/10/02)
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- Decarboxylation of 1-Aminocyclopropanecarboxylic Acid and Its Derivatives
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The question of whether the title compounds could be decarboxylated to cyclopropanone derivatives was answered in the affirmative by the following observations. (1) Compound 11a was decarboxylated by 1,2,3-indantrione in acetonitrile, benzene, or methanol.The initially formed intermediate could be trapped by N-phenylmaleimide (to form 3), by diethyl azodicarboxylate (to form an unstable adduct), by ninhydrin itself (to form 5) or by a proton (in methanol, to form 8). (2) Compound 11d was decarboxylated by phenylbis(trifluoroacetato-O)iodine to yield carbinolamine 12d.cis-2,3-Dideuterio-11d yielded cis-2,3-dideuterio-12d under the same conditions. (3) ACC was decarboxylated by phenanthroquinone to yield oxazole 9, probably by way of oxazoline 10.
- Vaidyanathan, Ganesan,Wilson, Joseph W.
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p. 1810 - 1815
(2007/10/02)
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- RHODIUM CATALYZED REDUCTIVE ESTERIFICATION REACTIONS
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Reductive esterification occurs when unsaturated acids are treated with hydrogen in alcohol using either rhodium trichloride or the dimer of chloro(1,5-hexadiene)rhodium(I) as the catalyst.Saturated acids containing appropriate functional groups are also esterified under the same conditions.
- Lin, Ivan J. B.,Zahalka, Hayder A.,Alper, Howard
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p. 1759 - 1762
(2007/10/02)
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