A novel amino acid racemization in vitamin b6-amino acid schiff base copper complexes: crystal structures of aquo (5'-phosphopyridoxylidene-dl-tyrosinato) copper(II) 3.5H2O and aquo (5'-phosphopyridoxylidene-dl-phenylalaninato) copper(II) 2.5H2O

A novel racemization observed in the Vitamin B6-amino acid Schiff base complexes, aquo (5'-phosphopyridoxylidene-l-tyrosinato) copper(II) and aquo (5'-phosphopyridoxylidene-l-phenylalaninato) copper(II) is described. The racemization taking place in solution under mild acidic conditions (pH 5-6) was confirmed by CD studies and the products were characterized by single crystal X-ray diffraction. The structures of both complexes show almost parallel orientation of the aromatic side chain and the pyridoxal II-system. The activation of the αCsingle bondH group due to the intermolecular II- interaction is probably the reason for the unusual racemization observed.

Racemization at proline residues during peptide bond formation : A study of diastereomeric mixtures of synthetic alamethicin fragments by 270 MHz 1H NMR

The stepwise synthesis of amino terminal pentapeptide of alamethicin, Z-Aib-Pro-Aib-Ala-Aib-OMe, by the dicyclohexylcarbodiimide mediated couplings leads to extensive racemization at the Ala and Pro residues. Racemization is largely suppressed by the use of additives like N-hydroxysuccinimide and 1-hydroxybenzotriazole. The presence of diastereomeric peptides may be detected by the observation of additional methyl ester and benzylic methylene signals in the 270 MHz 1H NMR spectra. Unambiguous spectral assignment of the signals to the diastereomers has been carried out by the synthesis and NMR studies of the D-Ala tetra and pentapeptides. The racemization at Pro is of particular relevance in view of the reported lack of inversion at C-terminal Pro on carboxyl activation.

``On-the-fly'' kinetics of enzymatic racemization using deuterium NMR in DNA-based chiral oriented media

We report the in situ and real-time monitoring of the interconversion of L- and D-alanine-d(3) by alanine racemase from Bacillus stearothermophilus directly observed by H-2 NMR spectroscopy in anisotropic phase. The enantiomers are distinguished by the difference of their H-2 quadrupolar splittings in a chiral liquid crystal containing short DNA fragments. The proof-of-principle, the reliability, and the robustness of this new method is demonstrated by the determination of the turnover rates of the enzyme using the Michaelis Menten model.

THE EFFECT OF MOBILITY OF MOLECULES ON RADIATION-INDUCED CHAIN SCISSION AND RACEMIZATION OF ISO-POLY(METHYL METHACRYLATE)

The radiation-induced chain-scission and racemization of isotactic poly(methylmethacrylate)(iso-PMMA) in amorphous and semi-crystalline state as well as in solution have been studied with nuclear magnetic resonance and molar mass deter-mination. It is shown that the chain-scission is dominant for iso-PMMA in dilute solution while the racemization reaction is not favorable in this case. On the contrary, the racemization is favorable when iso-PMMA was irradiated in its crystalline state while chain-scission is not. Such experimental results could be well explained by the mobility of molecules and "cage effect". The hypothesis, we proposed previously that the chain-scission, racemization and recombination are in competition and the final result depends on the state of molecular motion at which iso-PMMA was irradiated, has been verified verified once again.

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

omeprazole is a substituted benzimidazole which suppresses gastric-acid secretion by means of H+, K+-ATPase inhibition. It is an optically active drug with the sulfur of the sulfoxide being the chiral center. This pro-drug can be easily converted into its respective sulfenamide at low pH. In this work, omeprazole has been studied in relation to racemization barrier and decomposition reaction. Quantum chemistry coupled to PCA chemometric method were used to find all minimum energy structures. Conformational analysis and calculation of racemization barriers were carried out by PM3 semiempirical method (Gaussian 98). The average racemization energy barrier for all minimum energy structures (43.56 kcal mol(-1)) can be related to the velocity constant in Eyring's equation. The enormous half-life time at 100 degrees C (9.04 x 10(4) years) indicates that the process cannot be observed in human time scale. on the other hand, the difference of free energy change (Delta(Delta G) = -266.78 kcal mol(-1)) for the decomposition reaction shows that the process is favorable to the sulfenamide formation. The highly negative Delta(Delta G) obtained for the decomposition reaction shows that this process is extremely exothermic. This result explains why omeprazole decomposes and does not racemize. (C) 2008 Wiley Periodicals, Inc.

Aspartic acid racemization dating of Holocene brachiopods and bivalves from the southern Brazilian shelf, South Atlantic

The extent of racemization of aspartic acid (Asp) has been used to estimate the ages of 9 shells of the epifaunal calcitic brachiopod Bouchardia rosea and 9 shells of the infaunal aragonitic bivalve Semele casali. Both taxa were collected concurrently from the same sites at depths of 10 m and 30 m off the coast of Brazil. Asp D/L values show an excellent correlation with radiocarbon age at both sites and for both taxa (r(Site)(2) (9) (B. rosea) = 0.97 r(Site)(2) (1) (B.) (rosea) = 0.997, r(Site)(2) (9) (S.) (casali) = 0.9998, r(2) (Site) (1) (S.casali) = 0.93). The Asp ratios plotted against reservoir-corrected AMS radiocarbon ages over the time span of multiple millennia can thus be used to develop reliable and precise geochronologies not only for aragonitic mollusks (widely used for dating previously), but also for calcitic brachiopods. At each collection site, Bouchardia specimens display consistently higher D/L values than specimens of Semele. Thermal differences between sites are also notable and in agreement with theoretical expectations, as extents of racemization for both taxa are greater at the warmer, shallower site than at the cooler, deeper one. In late Holocene marine settings, concurrent time series of aragonitic and calcitic shells can be assembled using Asp racemization dating, and parallel multi-centennial to multi-millennial records can be developed simultaneously for multiple biomineral systems. (c) 2006 University of Washington. All rights reserved.

Amino acid racemization of Neogloboquadrina pachyderma from the Arctic Ocean

The long-term rate of racemization for amino acids preserved in planktonic foraminifera was determined by using independently dated sediment cores from the Arctic Ocean. The racemization rates for aspartic acid (Asp) and glutamic acid (Glu) in the common taxon, Neogloboquadrina pachyderma, were calibrated for the last 150 ka using 14C ages and the emerging Quaternary chronostratigraphy of Arctic Ocean sediments. An analysis of errors indicates realistic age uncertainties of about ±12% for Asp and ±17% for Glu. Fifty individual tests are sufficient to analyze multiple subsamples, identify outliers, and derive robust sample mean values. The new age equation can be applied to verify and refine age models for sediment cores elsewhere in the Arctic Ocean, a critical region for understanding the dynamics of global climate change.

Amino acid racemization for several DSDP samples (Table 1)

Kinetic parameters for the epimerization of isoleucine in multispecific foraminiferal asemblages were used to establish the effects of burial depth and the geothermal gradient on the extent of reaction. It was observed that with a little as thirty meters of burial in a normal thermal regime there were differences between the extent of epimerization measured and that which would have been predicted for thermal equilibrium with bottom water temperatures. As would be expected, these differences are greatest when the heat flow (the geothermal gradient) and/or the sedimentation rates are highest. These effects were observed in most of the DSDP samples studied, and have been used to estimate the average heat flux since the time of sample deposition. Occasional anomalous effects were observed which could not be related to past or present heat flux. These were determined to be due to such geologic occurrences as slumping and reworking or to recent sample contamination. Other problems emerged related to bottom water temperatures including changes over geologic time which are unknown and could not be deduced. Thus, the presence of epimerization anomalies in DSDP cores as noted above limits the effectiveness of amino acid geochronology in such cores, unless these anomalies can be recognized as ab initio.

Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of Asn(341), Tyr(60) and Phe(351) in tetrahydrofolate binding

SHMT (serine hydoxymethyltransferase), a type I pyridoxal 5'-phosphate-dependent enzyme, catalyses the conversion of L-serine and THF (tetrahydrofolate) into glycine and 5,10-methylene THE SHMT also catalyses several THF-independent side reactions such as cleavage of P-hydroxy amino acids, trans-amination, racemization and decarboxylation. In the present study, the residues Asn(341), Tyr(60) and Phe(351), which are likely to influence THF binding, were mutated to alanine, alanine and glycine respectively, to elucidate the role of these residues in THF-dependent and -independent reactions catalysed by SHMT. The N341A and Y60A bsSHMT (Bacillus stearothermophilus SHMT) mutants were inactive for the THF-dependent activity, while the mutations had no effect on THF-independent activity. However, mutation of Phe(351) to glycine did not have any effect oil either of the activities. The crystal structures of the glycine binary complexes of the mutants showed that N341A bsSHMT forms an external aldimine as in bsSHMT, whereas Y60A and F351G bsSHMTs exist as a Mixture of internal/external aldimine and gem-diamine forms. Crystal structures of all of the three Mutants obtained in the presence of L-allo-threonine were similar to the respective glycine binary complexes. The structure of the ternary complex of F351G bsSHMT with glycine and FTHF (5-formyl THF) showed that the monoglutamate side chain of FTHF is ordered in both the subunits of the asymmetric unit, unlike in the wild-type bsSHMT. The present studies demonstrate that the residues Asn(341) and Tyr(60) are pivotal for the binding of THF/FTHF, whereas Phe(351) is responsible for the asymmetric binding of FTHF in the two subunits of the dimer.

Specificity of protein - Nucleic acid interaction and the biochemical evolution

The water soluble carbodiimide mediated condensation of dipeptides of the general form Gly-X was carried out in the presence of mono- and poly-nucleotides. The observed yield of the tetrapeptide was found to be higher for peptide-nucleotide system of higher interaction specificity following mainly the anticodon-amino acid relationship (Basu, H.S. & Podder, S.K., 1981, Ind. J. Biochem. Biophys.,19, 251-253). The yield of the condensation product of L-peptide was more because of its higher interaction specificity. The extent of the racemization during the condensation of Gly-L-Phe, Gly-L-Tyr and Gly-D-Phe was found to be dependent on the specificity of the interaction -the higher the specificity, the lesser the racemization. The product formed was shown to have a catalytic effect on the condensation reaction. These data thus provide a mechanism showing how the specific interaction between amino acids/dipeptides and nucleic acids could lead to the formation of the lsquoprimitiversquo translation machinery.

Isoselenocyanates derived from Boc/Z-amino acids: synthesis, isolation,characterization, and application to the efficient synthesis of unsymmetrical selenoureas and selenoureidopeptidomimetics

Isoselenocyanates derived from Boc/Z-amino acids are prepared by the reaction of the corresponding isonitriles with selenium powder in presence of triethylamine at reflux. The utility of these new classes of isoselenocyanates in the preparation of selenoureidodipeptidomimetics possessing both amino as well as carboxy termini has been accomplished. The H-1 NMR analysis confirmed that the protocol involving the conversion of isonitriles to isoselenocyanates and their use as coupling agents in assembling selenour-eido derivatives is free from racemization. (C) 2010 Elsevier Ltd. All rights reserved.