Academic literature on the topic 'Γ Amino Acid'
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Journal articles on the topic "Γ Amino Acid"
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Hettasch, Joann M., Mark G. Bolyard, and Susan T. Lord. "The Residues AGDV of Recombinant γ Chains of Human Fibrinogen Must Be Carboxy-Terminal to Support Human Platelet Aggregation." Thrombosis and Haemostasis 68, no. 06 (1992): 701–6. http://dx.doi.org/10.1055/s-0038-1646347.
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SummaryThe carboxy-terminus of the γ chain of fibrinogen contains a sequence which is believed to be one of the domains that interacts with glycoprotein (GP) IIb/IIIa to support platelet aggregation. A normal variant of fibrinogen exists in which the four carboxy-terminal amino acids are replaced by 20 amino acids. This variant, known as γ’, has been reported to bind less effectively to platelets. The purpose of the present study was to engineer novel proteins to determine what differences in amino acid sequence between the γ and γ’ chains influence the interaction of the carboxyterminus with GPIIb/IIIa. In this regard, the γ chain cDNA in a bacterial plasmid expression vector was modified by oligonucleotide-directed mutagenesis to produce recombinant γ chains with amino acid changes in the carboxy-terminus which reflect the differences between γ and γ’. The recombinant γ chain with an unmodified carboxy-terminus supported adenosine diphosphate (ADP)-induced platelet aggregation to the same extent as intact fibrinogen. In contrast, the ability of γ’ 427 (the recombinant γ’ variant) and γ 427 (where the 16 amino acid γ’ extension [412–427] was added to the carboxy-terminus of γ) to support platelet aggregation was markedly reduced. In addition, the extent of ADP-induced platelet aggregation was decreased in the presence of γ’ 411 (where amino acids 408–411 in γ were replaced with amino acids 408–411 in γ’), while γ 407 (where the four carboxy-terminal amino acids were deleted) was not capable of supporting aggregation. These findings demonstrate that the four residues AGDV are not only required but must be carboxy-terminal to support platelet aggregation.
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Valachová, Dominika, Branislav Ferko, Eva Puchľová, Oľga Caletková, Dušan Berkeš, Andrej Kolarovič, and Pavol Jakubec. "Stereoselective Synthesis of syn-γ-Hydroxynorvaline and Related α-Amino Acids." Synthesis 51, no. 24 (October 16, 2019): 4568–75. http://dx.doi.org/10.1055/s-0039-1690705.
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The total syntheses of three enantiomerically pure non-proteinogenic amino acids, l-norvaline, γ-oxonorvaline, and syn-γ-hydroxynorvaline, are reported. The chromatography-free route pivoted on the construction of highly enantiomerically enriched substituted α-amino-γ-oxopentanoic acid, from which all three members were accessed divergently via chemoselective and stereoselective reductions. The rapid synthesis of this key α-amino-γ-oxopentanoic acid was achieved by a highly diastereoselective crystallisation-driven three-component Mannich reaction from the readily available building blocks acetone, glyoxylic acid monohydrate, and (S)-(4-methoxyphenyl)ethylamine. The enantiomeric purity of all target molecules was confirmed by HPLC analysis, either of the amino acids or their derivatives.
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Dutta, Arpita, Suven Das, Purak Das, Suvendu Maity, Prasanta Ghosh, and Soumya Shankha Biswas. "Unique supramolecular assembly of a synthetic achiral α, γ-hybrid tripeptide." Zeitschrift für Kristallographie - Crystalline Materials 237, no. 1-3 (March 1, 2022): 77–81. http://dx.doi.org/10.1515/zkri-2022-0002.
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Abstract An achiral tripeptide, namely, Boc-γ-Abu-m-ABA-Aib-OMe (γ-Abu: γ−amino butyric acid; m-ABA: meta-aminobenzoic acid) was synthesized by solution phase procedure. The α, γ-hybrid peptide was designed in such a way that two dissimilar γ−amino acids, one flexible and another rigid, were positioned sidewise along with α-amino isobutyric acid (Aib) as C-terminal residue. The single crystal X-ray diffraction analysis revealed that two kinks were generated around centrally placed m-ABA. Interestingly, the peptide self-assembled via three intermolecular N–H···O and one intermolecular C–H···O hydrogen bonding interactions to supramlecular helical architecture.
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Кудрявский, Дмитрий Леонович, Елена Константиновна Фомина, Людмила Юльевна Тычинская, Евгений Доминикович Скаковский, and Светлана Евгеньевна Богушевич. "NMR spectroscopy of Cu(II) complexes with acrylamide and sodium acrylate copolymer and ω-amino acids." Journal of the Belarusian State University. Chemistry, no. 1 (April 12, 2021): 85–98. http://dx.doi.org/10.33581/2520-257x-2021-1-85-98.
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Macromolecular complexes of acrylamide and sodium acrylate copolymer with microelements, including Cu(II), may form at preparation of crop protection and stimulation compositions, where the copolymer serves as an adhesive, water-retaining and film-forming agent. Preparations for crop production may also contain amino acids that protect plants under stressful conditions (cold, dry, etc.). Carboxylic groups of copolymer, carboxylic and amino groups of amino acids may be involved in mixed Cu(II) ions complexes formation. Number of methylene groups separating carboxylic and amino group of amino acids affects its ability to form a stable chelate cycle and, therefore, ligand composition of mixed Cu(II) ions complexes with acrylamide and sodium acrylate copolymer and amino acid. This work is aimed at determining the ligand composition of mixed macromolecular Cu(II) ion complexes with acrylamide and sodium acrylate copolymer and ω-amino acids (β-alanine, γ-aminobutyric acid, ε-aminocaproic acid). 13C and 1H NMR spectroscopy was used to clarify complexes composition. A complex where carboxylic groups of amino acids are ligands has been found to form in aqueous solutions of Cu(II) ions and ω-amino acid (β-alanine, γ-aminobutyric acid, ε-aminocaproic acid) at molar ratio of Cu(II) ions – amino acid equal to 1 : 6. A chelate complex where both carboxylic and amino groups of β-alanine are involved in coordination has been discovered to form in the solution containing Cu(II) ions, β-alanine, as well as acrylamide and sodium acrylate copolymer at molar ratio of Cu(II) – β-alanine – copolymer COO− equal to 1 : 6 : 30. Carboxylic groups of copolymer participate in complex formation as well. Carboxylic groups of both amino acids and the copolymer have been shown to participate in complex formation in aqueous solutions containing Cu(II) ions, either γ-aminobutyric or ε-aminokaproic acid and also acrylamide and sodium acrylate copolymer.
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Speranza, Giovanna, Marco Rabuffetti, Nikolina Vidović, and Carlo F. Morelli. "Synthesis of γ-Glutamyl Derivatives of Sulfur-Containing Amino Acids in a Multigram Scale via a Two-Step, One-Pot Procedure." Molbank 2020, no. 3 (July 10, 2020): M1147. http://dx.doi.org/10.3390/m1147.
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γ-Glutamyl derivatives of sulfur amino acids have been prepared in multigram scale starting from readily available starting materials. The synthesis comprises two one-pot operations, both consisting of two reactions. In the first operation, N-phtaloyl-l-glutamic acid anhydride is obtained from l-glutamic acid and phtalic anhydride. In the second one, N-phtaloyl-l-glutamic acid anhydride is used to acylate amino acids and the N-phtaloyl protecting group is removed. The described approach offers a viable entry to γ-glutamyl derivatives of sulfur-containing amino acids with flavor-enhancer and nutraceutical properties.
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Čeřovský, Václav, and Karel Jošt. "Enzymatically catalyzed synthesis of dipeptides of γ-carboxy-L-glutamic acid from benzyloxycarbonyl-γ-carboxy-DL-glutamic acid." Collection of Czechoslovak Chemical Communications 50, no. 4 (1985): 878–84. http://dx.doi.org/10.1135/cccc19850878.
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Enantioselective reaction of benzyloxycarbonyl-γ-carboxy-DL-glutamic acid with phenylhydrazides of various amino acids and with leucine, protected with various carboxy-protecting groups, has been studied.
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Zhu, Shaozhou, Cuiyu Gong, Dawei Song, Shuaihua Gao, and Guojun Zheng. "Discovery of a Novel (+)-γ-Lactamase from Bradyrhizobium japonicum USDA 6 by Rational Genome Mining." Applied and Environmental Microbiology 78, no. 20 (August 10, 2012): 7492–95. http://dx.doi.org/10.1128/aem.01398-12.
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ABSTRACTA novel (+)-γ-lactamase used for the resolution of racemic γ-lactam fromBradyrhizobium japonicumUSDA 6 was found as a result of sequence-structure guided genome mining. It consists of 409 amino acids, only 49% of which are identical to the amino acid sequences of the known (+)-γ-lactamase fromSulfolobus solfataricus. This is only the third (+)-γ-lactamase gene to be reported.
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Pataj, Zoltán, István Ilisz, Anita Aranyi, Enikő Forró, Ferenc Fülöp, Daniel W. Armstrong, and Antal Péter. "LC Separation of γ-Amino Acid Enantiomers." Chromatographia 71, S1 (February 5, 2010): 13–19. http://dx.doi.org/10.1365/s10337-010-1484-2.
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Onozato, Mayu, Kana Kobata, Tatsuya Sakamoto, Hideaki Ichiba, and Takeshi Fukushima. "LC–MS/MS Analysis of Thiol-Containing Amino Acids in Exosomal Fraction of Serum." Journal of Chromatographic Science 58, no. 7 (June 24, 2020): 636–40. http://dx.doi.org/10.1093/chromsci/bmaa028.
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Abstract It has been suggested that thiol-containing amino acids could be used as biomarkers for diseases associated with oxidative stress. We investigated the thiol-containing amino acids, homocysteine (Hcy), cysteine (Cys), glutathione (GSH) and γ-glutamylcysteine (γ-GluCys), in commercial human serum by using liquid chromatography–tandem mass spectrometry (LC–MS/MS) after precolumn derivatization with 4-fluoro-7-sulfobenzofurazan. This method was applied to determine the composition of thiol-containing amino acids in exosomes prepared from the serum. Hcy, Cys, GSH and γ-GluCys could be detected in the exosomal fraction, and the ratio of each thiol-containing amino acid was similar to those in the corresponding native serum. Cys (94.76%) was most enriched in the exosomal fraction, followed by GSH (2.97%), γ-GluCys (1.59%) and Hcy (0.68%). These findings suggest that thiol-containing amino acids, Hcy, Cys, GSH and γ-GluCys, are included in exosomes in human serum.
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Allan, RD, RK Duke, TW Hambley, GAR Johnston, KN Mewett, N. Quickert, and HW Tran. "Synthesis of Unsaturated Analogues of Glutamic Acid: Amination of Trianions From Unsaturated Dicarboxylic Acids With Chloramine." Australian Journal of Chemistry 49, no. 7 (1996): 785. http://dx.doi.org/10.1071/ch9960785.
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Trianions can be formed from dicarboxylic acids which contain a β,γ -double bond, and amination with chloramine yields β,γ-unsaturated α-amino acids. This methodology provides a convenient synthesis of amino acids that are inaccessible by other routes. (Z)-3-Phenylthiopent-2-enedioic acid and all four stable unsaturated analogues of the conformationally restricted glutamate analogue 1-aminocyclopentane-1,3-dicarboxylic acid have been synthesized to demonstrate the applicability of the method. The structure of one of the amino acid products, (�)-cis-1-aminocyclopent-4-ene-1,3-dicarboxylic acid (7), has been determined; it crystallizes in the space group P21/c, a 9.245(24), b 8.455(2), c 9.311(3) Ǻ, β 95.00(2)°, and the structure was refined to R 0.035 for 980 F.
Dissertations / Theses on the topic "Γ Amino Acid"
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Stanovych, Andrii. "Synthèse et études structurales de γ-peptides synthétisés à partir d’acides β,γ-diaminés." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112310/document.
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L’élaboration de nouveaux oligomères capables de mimer les propriétés des protéines naturelles est devenue un domaine de recherche très important, non seulement du point de vue structural mais aussi médicinal. Les peptides comportant des acides β-aminés ont été extensivement étudiés tandis que les recherches dans le domaine des γ-peptides sont plus récentes. Néanmoins, ces derniers montrent déjà des propriétés structurales uniques ainsi que des activités biologiques prometteuses.Dans notre laboratoire nous nous intéressons au développement d’une synthèse générale de nouveaux acides β,γ-diaminés à partir d’acides ∝-aminés naturels, notamment à la 3-déoxyaminostatine, et à leur utilisation dans la synthèse peptidique pour obtenir des peptides non-naturels afin d’étudier leurs propriétés conformationnelles. La stratégie de synthèse élaborée dans notre laboratoire et améliorée au cours de ces travaux a permis d’élargir la gamme des acides β,γ-diaminés. Deux diastéréomères cis et trans issus de la L-leucine, de la L- et D-phénylalanine ont été obtenus et engagés dans la synthèse de nouveaux peptides hybrides α/γ. Deux séries de peptides hybrides α/γ ont été étudiées. Les analyses structurales de la série comportant des acides ∝-aminés de configuration L montrent une capacité à adopter des structures secondaires bien définies, stabilisées par des liaisons hydrogènes intramoléculaires, impliquant notamment l’azote situé en β. De plus, une voie de synthèse vers un analogue d’un antibiotique naturel, le gramicidine S, a été proposée. Dans cet analogue, le motif D-Phe-L-Pro est remplacé par l’acide β,γ-diaminé issu de la D-phénylalanineThe design of a new oligopeptides, capable to mimic the properties of natural proteins, is an important field not only for structural studies but also in the developpement of new efficient drugs. The peptides featuring β-amino acids have been extensively explored, whereas the research in γ-peptides is more recent. The studies of γ-peptides show their ability to adopt stable secondary structures and also to have a promising biological activity. Our laboratory is interested in the synthesis of new β,γ-diaminoacids.The aim of this work is a developpement of new synthetic route starting from different natural α -amino acids and to use obtained β,γ-diaminoacids to access novel unnatural peptides having specific conformational properties.The synthetic strategy, developed and optimized in our laboratory during this work, gives access to diastereomers cis and trans from L-leucine, L- and D-phenylalanine which were used in the synthesis of a new hybrid α/γ-peptides. The structural studies were performed on two series of hybrid α/γ-peptides consisting of β,γ-aminoacid from L-leucine and L- or D-α-amino acids. In the first case, the peptides are able to adopt stable secondary structures stabilized by intramolecular hydrogen bonds involving the nitrogen on the β-position. In addition, we present the synthesis of an analogue of gramicidine S, a naturally occuring antibiotic cyclic peptide. The dipeptide pattern D-Phe-L-Pro has been replaced with the β,γ-diaminoacid synthesized from D-phenylalanine
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Bonnel, Clément. "Oligopeptides construits autour du γ-aminoacide ATC : synthèses, analyses structurales et évaluation biologique." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT201.
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Les travaux décrits dans ce manuscrit concernent la synthèse, l’étude structurale et l’évaluation biologique d’oligopeptides abiotiques incorporant le gamma-aminoacide hétérocyclique nommé ATC (acide-4-Aminométhyl-1,3-Thiazole-5-Carboxylique). Les ATCs sont construits autour d’un noyau thiazole et présentent deux points de diversité structurale. De précédents travaux ont déterminé que la présence du noyau thiazole entre les positions alpha et béta bloquait l'angle zéta autour de 0°, structurant les homo-oligomères de poly-(S)-ATCs en une hélice 9 droite et les faisant ainsi entrer dans le domaine des foldamères. Dans une première partie, nous avons entrepris de développer une voie de synthèse simple, flexible et énantiosélective permettant d’obtenir les ATCs stéréochimiquement purs sur une échelle de plusieurs grammes à partir d'alpha-aminoacides commerciaux. L’introduction de la diversité chimique est réalisée via deux étapes-clés que sont la condensation croisée de Claisen et la réaction de cyclisation de Hantzsch. Puis l’identification des marqueurs de structuration RMN et IR-TF des oligomères d'ATCs a été mise à profit pour caractériser le repliement d’hétéro-oligomères combinant ATCs et alpha-aminoacides. Ainsi, une étude structurale par RMN, IR-TF, cristallographie RX et dichroïsme circulaire a démontré que l’enchaînement 1:1 (L)-alpha:(S)-ATC se structurait en un ruban, stabilisé par un réseau intramoléculaire de liaisons hydrogène bifides formant des pseudocycles à 9 et 12 chaînons. La distribution des chaînes latérales le long du squelette principal présente une forte analogie avec l’hélice alpha, ce qui pourrait constituer un atout majeur pour le développement de composés à finalité thérapeutique. La dernière partie de ce travail a porté sur la conception de pseudo-peptides amphipatiques pour des applications en temps qu'antimicrobiensThis manuscript describes the synthesis, the structural study and the biological evaluation of abiotic oligopeptides incorporating the heterocyclic gamma-amino acid ATC (4-Aminomethyl-1,3-Thiazole-5 Carboxylic acid). This original block is built around a thiazole ring and displays two lateral chains. Previous work in our laboratory highlighted that the presence of the thiazole ring between the positions alpha and beta implied that zeta angle was blocked around 0°, thus structuring poly-(S)-ATCs homo-oligomers in a right-handed 9-helix foldamer. First, development of a simple, flexible and enantioselective synthesis on a few grams scale has allowed to get access of a highly diverse ATC library from commercial alpha-amino acids. Introduction of the chemical diversity occurs via two key steps implying a cross-Claisen condensation and a Hantzsch cyclization. Then identification of NMR and FT-IR structural markers of ATC-containing oligomers was used to characterize the folding propensity of hybrid α:ATC oligomers. We demonstrated that 1:1 (L)-alpha:(S)-ATC heterochiral oligomers are structured in solution in a new ribbon-like shape stabilized by a bidentate intramolecular hydrogen bond network forming 9- and 12-membered pseudorings. The distribution of lateral chains along the main skeleton shows a high analogy with alpha-helix thus constituting a major advantage for potential medicinal applications. The last part of this work has focused on the design of amphipathic ATC-containing pseudo-peptides as antimicrobial agents
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Wenjie, Lu. "Synthesis and Evaluation of Functionalized Dirhodium(II) Carboxylate Catalysts Bearing Axially Chiral Amino Acid Derivatives." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225528.
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Wersinger, Eric. "Inhibition présynaptique et contraste dans la rétine de souris : à la recherche du rôle des dystrophines." Paris 6, 2007. http://www.theses.fr/2007PA066122.
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Ce travail visait à étudier la neurotransmission dans la première synapse de la rétine, ou l’inhibition latérale permet un renforcement du contraste spatial et de la perception des bords des objets. Or, la nature de son mécanisme n’est pas connue à ce jour. L’utilisation de techniques d’électrophysiologie, d’immunohistochimie et de biologie moléculaire nous a permis de démontrer, à partir d’une étude comparative sur quatre souches de souris, qu’une forte proportion de cellules horizontales expriment la GAD65, mais contiennent du GABA uniquement chez la souris Balb/c. Notre approche pour mettre en évidence une transmission GABA, a permis de révéler la présence du transporteur du glutamate EAAT5 dans les cellules bipolaires à bâtonnet. Son activation permet un rétrocontrôle rapide renforçant le contraste dans la voie des bâtonnets. Enfin, nous avons apporté de nouveaux éléments pour comprendre le rôle des dystrophines dans la première synapse, et dont l’absence conduit à un défaut de transmission.
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Olszewski, Tomasz Krzysztof. "Original syntheses of new biomolecules : from imidazole and thiazole derivatives of α-aminophosphonic acids and γ-amino-α, β-dihydroxy carboxylic acid derivatives to disaccharide mimics." Montpellier 2, 2006. http://www.theses.fr/2006MON20017.
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Flanigan, David L. Jr. "Studies in Rhodium Catalyzed Intramolecular C-H Insertion of Amino Acid Derived α-Diazo-α-(substituted)acetamides and its Application to the Total Synthesis of clasto-Lactacystin β-Lactone." Scholar Commons, 2004. https://scholarcommons.usf.edu/etd/1037.
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Lactacystin is a microbial metabolite isolated by Omura that exhibits neurotrophic activity in neuroblastoma cell lines. Lactacystin and especially its β-lactone analog are the first examples of non-polypeptide small molecules capable of specifically inhibiting the 20S proteasome. Various asymmetric total syntheses of lactacystin and its analogs have been reported. The total synthesis of clasto -lactacystin β-lactone is achieved using L-serine methyl ester as the starting material and the sole source of stereochemical induction. The success of this synthesis hinges on two featured transformations. The first key step involves formation of the γ -lactam core via rhodium (II) catalyzed intramolecular C-H insertion of the α-diazo-α-(phenylsulfonyl)acetamide intermediate. The methodology for this transformation has been developed and applied to the synthesis of highly functionalized stereogenic γ-lactams from natural α-amino acids. Three control elements that govern γ-lactam formation are described. This step is highlighted by the xvi simultaneous creation of two stereogenic centers of the γ-lactam core. The second key step involves the late stage aldol coupling for quaternary carbon formation and installation of the hydroxyisobutyl group. In all previously reported syntheses, this is the very first aspect which is addressed. The stereochemical outcome of this step is directed by the chiral environment of the enolate itself. Various attempts to achieve selectivity are explored and reported. Completion of the synthesis of clasto-lactacystin β-lactone requires 17 steps with an overall yield of 10%. Some general attempts for optimizing the synthetic scheme are discussed as well as the future direction of this research.
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Wan, Yang. "Synthesis of β,γ-diamino acids and their use to design new analogues of the antimicrobial peptide Gramicidin Septide antimicrobien, la Gramicidine S." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS407/document.
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Dans notre groupe, nous nous intéressons au développement de peptides contenant des acides γ-aminés. Comme d’autres peptides contenant des acides aminés non naturels, ils ont montré leur capacité à posséder des conformations stables et/ou des propriétés biologiques intéressantes. De plus, ces peptides sont généralement résistant à la protéolyse. Dans l’objectif de synthétiser des acides -diaminés sous la forme d’un seul stéréoisomère, nous avons développé une voie de synthèse reposant sur une réaction de Blaise suivie d’une réduction diastéréosélective. En appliquant cette méthode, nous avons synthétisé des acides β,γ-diaminés dérivés de la D-phénylalanine et de l’acide L-glutamique. Le premier a été utilisé pour concevoir des analogues d’un peptide antimicrobien, la gramicidine S. Comparé à la molécule parent, les analogues ont montré une cytotoxicité beaucoup moins importante pour les cellules hôtes tout en conservant une activité antibactérienne intéressante. Cette étude nous a donné de meilleures connaissances pour développer d’autres analogues de la gramicidine S ainsi que d’autres peptides antimicrobiens. Nous avons également effectué de nombreuses optimisations pour synthétiser de façon efficace des acides β,γ-diaminés cycliques à partir de l’acide L-glutamique. Les oligomères incorporant ces acides β,γ-diaminés et des acides α-aminés ont montré un fort potentiel pour l’adoption de conformations stables. Ces études vont être poursuiviesIn our group, we are interested in developing peptides containing β,γ-diamino acids . Along with many other peptides containing unnatural amino acids, they have shown the ability to possess stable conformations and/or interesting biological activities. Moreover, those peptides are usually more resistant to proteolysis. In order to synthesize stereopure γ-amino acids, we have developed a synthetic route using Blaise reaction and subsequent diastereoselective reduction as key reactions. Through applying this method, we have synthesized β,γ-diamino acids derived from D-phenylalanine and L-glutamic acid. The former β,γ-diamino acid was used for designing antimicrobial peptide gramicidin S analogues. Compared with mother molecule, the analogues exerted much less host cell cytotoxicity while remaining interesting antibacterial activity. Meanwhile, it gave us more knowledge for further developing analogues of gramicidin S as well as other antimicrobial peptides. We also paid lots of effort to efficiently synthesize cyclic β,γ-diamino acids starting from L-glutamic acid. Interestingly, when oligomers incorporating this β,γ-diamino acids and α-amino acids, they have shown the potential to adopt stable conformations. The following studies will be continuously investigated
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Zammit, Charlotte Maria. "Asymmetric synthesis of β- and γ- amino acids." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:35138286-c217-4d28-990b-941149b5daa5.
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This thesis is concerned with the development of new synthetic routes for the asymmetric syntheses of a range of β- and γ-amino acids. Chapter 1 introduces the various biological activities displayed by cyclic β-amino acid containing compounds together with their occurrence in pharmaceutical molecules and β-peptides. Some of the most commonly used synthetic strategies for the preparation of carbocyclic β-amino acids are briefly described, with the focus on the formation and functionalisation of a five-membered carbocyclic ring. Chapter 2 describes a full investigation into a highly diastereoselective Ireland-Claisen rearrangement of stereodefined allyl β-amino esters to access enantiopure α-substituted β-amino acid products. The synthetic utility of this methodology is highlighted by its application in the asymmetric syntheses of five previously inaccessible C(5)-substituted 1,2-anti-1,5-syn-transpentacins. Chapter 3 delineates investigations into a highly diastereoselective conjugate additionelimination protocol for the preparation of a cyclic β'-amino-α,β-unsaturated ester. Subsequent chemo- and diastereoselective conjugate addition reactions of Grignard reagents and lithium amides to this substrate enabled the asymmetric syntheses of four C(5)-substituted 1,2-anti-1,5-syn-transpentacins and two five-membered β,β'-diamines. Chapter 4 details the extension of the protocol developed in Chapter 3 for the conjugate addition of Grignard reagents to a range of acyclic γ-(N,N-dibenzylamino)-substituted α,β-unsaturated esters. Elaboration of the β,γ-disubstituted γ-amino ester products culminated in the asymmetric syntheses of six β,γ-disubstituted γ-amino acids. Chapter 5 chronicles the preparation of an azabicyclic α,β-unsaturated ester, following which attempts towards the asymmetric synthesis of various substituted pyrrolizidines using a conjugate addition protocol are subsequently described. Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3, 4 and 5.
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Hallinan, Keith Oliver. "Synthetic and metabolic studies on β,γ-unsaturated α-amino acids." Thesis, University of Warwick, 1992. http://wrap.warwick.ac.uk/110385/.
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(1) Chapter three describes the attempted investigation of the mechanism of cepham formation catalysed by the enzyme isopenicillin N synthase of Acremonium cephalosporium. The stereochemistry of this cyclisation was to be investigated with a specifically labelled butyrate residue in the unnatural substrate. 8-(a-amino) adipoyl-cysteinyl- a-aminobutyric acid. The chiral methyl and methylene groups were to be synthesised by the tritiation of specifically deuterated vinylglycine. This, in turn, was to be prepared from phenyl (2-lrimcthylsilylethynyl) sulphone. Scrambling of the deuterium labelling occurred in this synthesis of vinylglycine and so forced the abandonment of the experiment without concluding the investigation. (2) Chapter four describes the preparation of vinylglycine in a simple, inexpensive, three step synthesis. The synthetic pathway involved a Pinner reaction, sodium hypochlorite treatment and an aqueous Neber rearrangement. The overall yield was 52% from the vinylcyanide. This method was applied to the production of other b.y-unsaturated a-amino acids with mixed success. The resolution of the r-butyloxycarbonyI derivatives of the amino acids so prepared was investigated with the thiol protease, papain. Ethyl L-N-t-butyloxycarbonylvinylglycine prepared in this manner was transformed by epoxidation, dihydroxylation and cyclopropylation. An attempt to prepare a fluorothreonine derivative from the epoxide gave only the 2.3-dehydrohomoserine analogue. (3) Chapter five describes the development of methyl (R)-(2-2H)- N-4-mcthoxyphcnylglycinatc (I) as a potential reagent for determining enantiomeric excess in chiral acids. The diastereomera formed differ only in isotopic stereochemistry, thus the possibility of kinetic resolution is reduced to a minimum. The ee is measured by the proton nmr spectrum of the diastereomera. In coupling (I) to a range of racemic chiral carboxylic acids the expected 1:1 ratio was observed. However during one of the steps in the preparation of (I) racemisation of the proton label occurred thus a single diastcrcomcr has yet to be prepared.
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Kerres, Sabine Martha [Verfasser], and Oliver [Akademischer Betreuer] Reiser. "Synthesis of γ-cyclobutane amino acids via visible light / Sabine Martha Kerres ; Betreuer: Oliver Reiser." Regensburg : Universitätsbibliothek Regensburg, 2019. http://d-nb.info/1196873410/34.
Full textBooks on the topic "Γ Amino Acid"
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Pearl, Phillip L., and William P. Welch. Pediatric Neurotransmitter Disorders. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0059.
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The pediatric neurotransmitter disorders represent an enlarging group of neurological syndromes characterized by inherited abnormalities of neurotransmitter synthesis, metabolism, and transport. Disorders involving monoamine synthesis include guanosine triphosphate cyclohydrolase deficiency (Segawa disease or classical Dopa-responsive dystonia as the heterozygous form), aromatic amino acid decarboxylase deficiency, tyrosine hydrolase deficiency, sepiapterin reductase deficiency, and disorders of tetrahydrobiopterin synthesis. These disorders can be classified according to whether they feature elevated serum levels of phenylalanine. Disorders of γ-amino butyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase deficiency and GABA-transaminase deficiency. Glycine encephalopathy is typically manifested by refractory neonatal seizures due to a defect in the glycine degradative pathway. Pyridoxine-responsive seizures have now been associated with deficiency of α-aminoadipic semialdehyde dehydrogenase as well as a variants requiring therapy with pyridoxal-5-phosphate and folinic acid.
Book chapters on the topic "Γ Amino Acid"
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Hanrahan, Jane R., and Graham A. R. Johnston. "Synthesis of γ-Aminobutyric Acid Analogs." In Amino Acids, Peptides and Proteins in Organic Chemistry, 573–689. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2010. http://dx.doi.org/10.1002/9783527631766.ch14.
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ffrench-Constant, R. H., H. G. Zhang, and M. B. Jackson. "Biophysical Analysis of a Single Amino Acid Replacement in the Resistance to Dieldrin γ-Aminobutyric Acid Receptor." In ACS Symposium Series, 192–204. Washington, DC: American Chemical Society, 1995. http://dx.doi.org/10.1021/bk-1995-0591.ch012.
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Tung, Roger D., Chong-Qing Sun, Don Deyo, and Daniel H. Rich. "Asymmetric syntheses of β-OH and β-OH, γ-alkyl α-amino acids: Analogs of the unusual cyclosporin amino acid MeBmt." In Peptides, 149–51. Dordrecht: Springer Netherlands, 1988. http://dx.doi.org/10.1007/978-94-010-9595-2_43.
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Kumar, Antul, Anuj Choudhary, Harmanjot Kaur, Mohammed Javed, and Sahil Mehta. "Plant Performance and Defensive Role of γ-Gamma Amino Butyric Acid Under Environmental Stress." In Plant Performance Under Environmental Stress, 277–99. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-78521-5_11.
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Langford, Marlyn P., Thomas B. Redens, and Donald E. Texada. "Excitatory Amino Acid Transporters, Xc− Antiporter, γ-Glutamyl Transpeptidase, Glutamine Synthetase, and Glutathione in Human Corneal Epithelial Cells." In Oxidative Stress in Applied Basic Research and Clinical Practice, 67–82. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1935-2_4.
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Furukawa, Tadayasu, and Takahiro Hara. "Potential of γ-L-glutamyl-L-glutamine as an L-glutamine-containing dipeptide for parenteral nutrition." In Amino Acids, 1114–18. Dordrecht: Springer Netherlands, 1990. http://dx.doi.org/10.1007/978-94-011-2262-7_140.
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Molnár, László, Gábor Kiszler, Edit Pollák, and László Deres. "Distribution pattern of γ-amino butyric acid immunoreactive neural structures in the central and peripheral nervous system of the tubificid worm, Limnodrilus hoffmeisteri." In Aquatic Oligochaete Biology IX, 33–43. Dordrecht: Springer Netherlands, 2006. http://dx.doi.org/10.1007/1-4020-5368-1_4.
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Grübler, G., S. Stoeva, H. Echner, and W. Voelter. "A convenient, straightforward solid phase synthesis of γ-endorphin on polystyrene matrix,grafted with polyoxyethylene spacer arms, using Fmoc amino acid N-carboxy anhydrides." In Peptides, 51–53. Dordrecht: Springer Netherlands, 1994. http://dx.doi.org/10.1007/978-94-011-0683-2_10.
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Trabocchi, Andrea, Gloria Menchi, and Antonio Guarna. "Synthesis of γ- and δ-Amino Acids." In Amino Acids, Peptides and Proteins in Organic Chemistry, 527–71. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2010. http://dx.doi.org/10.1002/9783527631766.ch13.
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Blaskovich, M. A., A. W. Wong, and G. A. Lajoie. "Synthesis of optically enriched β,γ-unsaturated α-amino acids." In Peptides 1994, 205–6. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-1468-4_85.
Full textConference papers on the topic "Γ Amino Acid"
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"Computational study of CO2 solubility in amino acid-based ionic liquids using COSMO-RS." In Sustainable Processes and Clean Energy Transition. Materials Research Forum LLC, 2023. http://dx.doi.org/10.21741/9781644902516-33.
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Abstract. The carbon capture, use, and sequestration (CCUS) techniques are proven to be efficient at lowering the atmospheric concentration of carbon dioxide. Notwithstanding the advances in this area, there are still significant restrictions in carbon dioxide (CO2) capture techniques in industry such as high capital costs, solvent evaporation losses, and low absorption and desorption rates. Ionic liquids (ILs) have received much interest as green solvent due to the benefits of their distinctive properties such as low vapor pressure and their capacity to capture CO2 making them a suitable replacement for present solvents, such as amines. Amino acid based ILs having close similarity with the alkanolamines may potentially have high affinity for CO2 absorption. Nevertheless, available database on these ILs is still limited and only focus on the common types of amino acids. Therefore, this paper aims to predict the CO2 absorption of different amino acid-based ionic liquids as cation/anion using quantum chemical calculation tools namely Conductor like Screening Model for Real Solvents (COSMO-RS) and TURBOMOLE. We evaluated 84 different ILs of different cations and anions based on their CO2 capacity, activity coefficient at infinite dilution (γ∞), and Henry’s constant (H). The results showed that amino acid as anions significantly enhanced the CO2 solubility compared to amino acid as cations. However, glycinium tetrafluoroborate [Gly+][BF4] showed high affinity for CO2 absorption compared to other amino acid-cations based with activity coefficient at infinite dilution (γ∞) = 0.117 and (H) = 8.07. We showed that the selection of anions/cations can significantly change the CO2 capacity in ILs.
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Terukina, S., M. Matsuda, N. Yoshida, K. Yamazumi, Y. Takeda, and T. Takano. "TWO ABNORMAL FIBRINOGENS DESIGNATED AS OSAKA II AND MORIOKA WITH A HITHERTO UNIDENTIFIED AMINO ACID SUBSTITUTION; γARG-275 BY CYS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644701.
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A hitherto unidentified amino acid substitution of γ Arg-275 by Cys has been found in two abnormal fibrinogens, Osaka II and Morioka. The propositi are both asymptomatic heterozygotes for the abnormality characterized by altered polymerization of fibrin monomers. Reducing SDS-PAGE revealed that fibrinogens derived from thé propositi both consist of two populations; one with a normal and the other with an abnormal longer γ-chain by 0.5 Kd.The γ-γ cross-linking took place nearly normally, however. Analyzing plasmic digests of fibrinogen by SDS-PAGE, we located the abnormality residing in the γ-chain remnant of fragment D. Chromatofocusing of D1 obtained by plasmic digestion in 5 mM Ca++ of purified fibrinogen separated the variant D1 (vD1) from the normal one (nD1) distinctly, as confirmed by SDS-PAGE and functional studies. As anticipated, vD1 failed to interfere with normal fibrin polymerization and thrombin clotting of normal fibrinogen, whereas nD1 inhibited these reactions significantly. After reduction and pyridylethylation, vD1 and nD1 were individually digested with lysylendopeptidase (lysEP). Analyzing the digests by reverse phase HPLC, we noted a single peak present in the digests of vD1 but missing in those of nD1, and vice versa. Analysis of N-terminal five cycles of these peptides suggested that both of them corresponded to the peptide with residues 274302 based on the known sequence data. Primary sequence and total amino acid analyses revealed that γ Arg-275 has been substituted by Cys in both of these abnormal fibrinogens. Analysis of the lysEP-digests of the isolated γ-chain also gave the same result. Since no free SH has been identified at the γ Cys-275 substitute, the variant γ-chain may be endowed with some additive by an S-S linkage. Even if so, elucidation of an apparent elongation by SDS-PAGE of the γ-chain variant must await further investigation. In any case, however, the substitution of γ Arg-275 by Cys may have induced critical alterations in the γ-chain-dependent polymerization site in the D domain in these two abnormal fibrinogens.
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Yoshida, N., S. Terukina, M. Matsuda, M. Moroi, M. Okuma, and N. Aoki. "FIBRINOGENS KYOTO AND TOCHIGI, EACH WITH AN APPARENT ABNORMAL MOL. WT. γ CHAIN, ARE CHARACTERIZED BY REPLACEMENT OF γ ASN-308 BY LYS AND γ ARG-275 BY CYS, RESPECTIVELY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644702.
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Congenital inherited abnormal fibrinogens (Fbgs) Kyoto and Tochigi showed prolonged thrombin- and reptilase-time, normal release of fibrinopeptides A and B, normal cross linking ability and impaired polymerization of the fibrin monomer.Purified Fbg analyzed on SDS-PAGE under the reduced condition in the system of Laemmli contained 50 % of an apparent lower mol. wt. γ chain (γ Kyoto)(mol. wt.= 48,000 compared with 50,000 for the normal) in Fbg Kyoto and an apparent higher mol. wt. γ chain (γ Tochigi)(mol. wt.= 50,500) in Fbg Tochigi. Apparent mol. wt. differences were also detected in reduced and carboxymethyl ated Fbg, Fbg fragment D1, and D2, but not in D3. This suggested that the abnormality of γ chains in both Fbgs is in γ 303-356.Amino acid sequence analysis was performed for CNBr- or lysylendopeptidase-digested peptides of the γ chain or D1 peptides after fractionation on HPLC. In Fbg Kyoto, γ Asn-308 was substituted by Lys, and a deletion of short peptides corresponding to the mol. wt. difference of 2,000 could not be detected. In Fbg Tochigi, γ Arg-275 was substituted by Cys, and no abnormality of amino acid sequence was found in γ 303-356.These results suggest that some lesions or conformations containing γ 275 and γ 308 will directly or indirectly affect polymerization of fibrin monomers. Although the reason for apparent mol. wt. differences is not known yet, SDS-PAGE in the system of Laemmli will be useful for the analysis of abnormal Fbgs.Fbg Kyoto could not be separated into two or three populations and may contain hetero-dimer molecules, but Fbg Tochigi had unclottable Fbg with predominant γ Tochigi and may contain abnormal homo-dimer molecules and normal molecules.
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Andrieux, A., M. H. Charon, G. Hudry-Clergeon, and G. Marguerie. "FIBRINOGEN SEQUENCES INTERACTING WITH PLATELET GPIIbIIIa." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643519.
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Fibrinogen (Fg), fibronectin (Fn) and von Willebrand factor (vWF), interact with GPIIbllla on AD? stimulated platelets, and a common mechanism has been postulated for the binding of these adhesive proteins. Fg, Fn and vWF contain the tripeptide Arg-Gly-Asp and synthetic analogues to this sequence inhibit their interaction with platelet and their concomitant adhesive reactions. On the other hand, sequences corresponding to the Fg γ chain inhibit the binding of Fg, Fn and vWF to platelet and may also represent a potential recognition site. This raises the possibility that the γ chain sequence and Arg-Gly-Asp interact with the same site or represent primary and secondary sites for the Fg molecule. Within this context, the capacity of these sequences to interact with GPIIbllla and to block fibrinogen binding were compared. The smallest γ chain sequence that was active in inhibiting this reaction was the hexamer Lys-Gln-Ala-Gly-Asp-Val corresponding to the last six amino acid residues at the C-terminus of the γ chain. In parallel, peptides with the structure Arg-Gly-Asp-X were synthesized and tested in vitro. The activity of these peptides was dependent upon the hydrophobicity of the amino acid residue at position X. Arg-GLy-Asp-Phe corresponding to the sequence at position 95-98 in the Fg Aα chain was 5 to 10 times more active than Arg-GLy-Asp-Ser, present at position 572-575 in the Aα chain, and was 10 to 20 times more active than the γ chain hexamer. Both the Aα chain and γ chain sequences however, inhibited Fg binding by greater than 90%. When the γ chain sequence and the Arg-Gly-Asp-X sequence were coupled to Sepharose, GPIIbIIIa interacted with these sequences and was eluted from each column by either of the peptides. Finally direct binding experiments indicated that Arg-Gly-Asp-X and γ chain sequences are competitive antagonists. These results suggest that both sequences interact with the same site on GPIIbIIIa and comparison of the hydrophilicity of these peptides suggests that the binding domain on GPIIbIIIa exhibits hydrophobic properties.
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Stenflo, J., A.-K. öhlin, Å. Lundvall, and B. Dahlback. "β-HYDROXY ASPARTIC ACID AND ft-HYDROXYASPARAGINE IN THEEGF-HOMOLOGY REGIONS OF PROTEIN C AND PROTEINS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643995.
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The amino acid sequence has been determined for all of the vitamin K-dependent proteins and the gene structure is known for some of them. These findings have shown the proteins to consist of four clearly discernible domains, except protein S which has six domains. The protein domains seem to be coded on separate exons (Foster, D. C. et. al. 1985 Proc. Natl. Acad. Sci. USA 82,4673). The vitamin K-dependent γ-carboxyglutamic acid (Gla) containing domain isthe common structural denominator of the members of this protein family. In addition, all of these proteins except prothrombin contain domains that are homologous to the precursor of the epidermal growth factor (EGF). Such domains arealso found in proteins that are not vitamin K-dependent, such as the low density lipoprotein receptor, thrombomodulin, factor XII, plasminogen, the tissue type plasminogen activator, urokinase and the complement protein Clr. The vitamin K-dependent proteins can be dividedinto three groups. Factors VII, IX, X, protein C and protein Z form one group, which in addition to the Gla-region have two EGF-homology regions and one domain that is homologous to the serine proteases. Prothrombin has two 'kringle' structures and a serine protease domain and constitutes a group of its own. Protein S is also unique in that it has four EGF-homology regions and a COOH-terminal region that is homologous to the sexual hormone binding globulin (see poster by Edenbrand et. al.).Recently a posttranslationally modified amino acid, B-hydroxyaspatic acid (Hya), was identified in position 71 in the NH2-terminal EGF-homology region ofbovine protein C. The amino acid is formed by hydroxylation of aspartic acid. It has also been identified in the corresponding positions in factors VII, IX,X and protein Z (i. e. proteins which like protein C have two EGF-homology regions each). In protein S the N2-terminal of four EGF-homology regions has hydroxy lated aspartic acid .whereas the following three EGF-like domains have B-hydroxyasparagine. The nucleotide sequence codes for asparagine in the three latter positions. Neither vitamin K nor vitamin C seem to be involvedin the formation of the two hydroxylated amino acids. Recently, Hya was identified in acid hydrolysates of the complement protein Clr. Hya and Hyn have onlybeen found in domains that are homologous to the EGF precursor. In an attempt to identify the structural requirement of the hydroxylating enzyme, we have compared the sequences of EGF-homology regions that contain Hya or Hyn with the corresponding sequences that have been shown not to contain the modified amino acids. The domains that have Hya or Hyn have the consensus sequence Cx xxxx xCxC. This sequence has been found in three EGF-like domains in the EGF-precursor, in two in the LDL-receptor and in two in thrombomodulin. Furthermore, the neurogenic Notch locus in Drosophila melanogaster codes for 36 EGF-homolgy regions, 22 of which contain the consensussequence, whereas the Lin-12 locus in Caenorhabditis elegans codes for at least 11 EGF-like repeats, two of which comply with the consensus sequence. Whether any of these proteins contain Hya orHyn is not yet known with certainty.It has been hypothesized that Hya isinvolved in the Gla independent Ca2+binding of factors IX, X and protein C. In an attempt to resolve this issue, we have isolated the EGF-homology region from human protein C and been able to demonstrate that it binds Ca2+ (see poster by öhlin and Stenflo). However, we do not yet know whether Hya is directly involved in the Ca2+binding.
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Wilhelm, O., A. Henschen, R. Hafter, and H. Graeff. "TUMOR-ASSOCIATED FIBRINOLYSIS IN OVARIAN CARCINOMA - HPLC AND N-TERMINAL AMINO ACID ANALYSIS REVEAL THE PATHWAY OF DEGRADATION OF CROSSLINKED FIBRIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643189.
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Crosslinked fibrin has been demonstrated by immunohistochemi-cal tests to occur around tumor plugs, on the surface and in the stroma of the tumor in ovarian cancer. High levels of D-Dimer (200-800μg/ml), the characteristic terminal degradation product of crosslinked fibrin, are found in ascitic fluid of patients with advanced ovarian cancer. These findings suggest that fibrin polymerisation and degradation are related to and even may influence tumor growth. The kind of proteases which are responsible for degradation of crosslinked fibrin is, however, unknown.lt was the aim of this study to evaluate whether plasmin and/or other proteases are involved in tumor-associated fibrinolysis. Therefore the total high-molecular-weight fibrin degradation products in ascitic fluid were purified by protamine sulfate precipitation, gel filtration, immunoadsorption and compared with the components of plasmin-degraded crosslinked fibrin, i.e. DD,DY,YX,DXD and DXY, by direct SDS-PAGE in the absence of mercaptoethanol and after excision of the bands, mercaptolysis and re-electrophoresis. Pronounced similarity between the two sets of fragments was observed. For further information the fragments from the two sources were mercaptolysed and their polypeptide chain components separated by reversed-phase high-performance liquid chromatography, the components being identified by N-terminal sequence analysis and SDS-PAGE. Highly similar patterns were obtained and components corresponding to γ-γ ,γ-γ1, β, β2 and α1 could be recognized. The findings provide strong evidence for plasmin being the primary protease involved in ovarian carcinoma-related fibrinolysis, (supported by Deutsche Forschungsgemeinschaft.SFB 207, A2).
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Kostić, Marina, Vera Divac, and Sven Mangelinckx. "SYNTHESIS AND CHARACTERIZATION OF PALLADIUM (II)–2- (AZIDOMETHYL)CYCLOPROPANE-1,1-DICARBOXYLIC ACID COMPLEX." In 1st INTERNATIONAL Conference on Chemo and BioInformatics. Institute for Information Technologies, University of Kragujevac, 2021. http://dx.doi.org/10.46793/iccbi21.297k.
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The discovery that palladium complexes possess a wide range of biological activities (from antitumor, -viral, -malarial, -fungal to antimicrobial activities) encourages further research in this scientific field. Herein we describe the synthesis and characterization of a novel palladium (II) complex, using [Pd(dien)Cl]Cl and 2-(azidomethyl)cyclopropane-1,1-dicarboxylic acid (azmcpda) as a ligand. [Pd(dien)Cl]Cl was selected as a starting material taking into consideration its importance as a model for the investigation of the substitution reactions in coordination chemistry and a deeper understanding of the biological activities of some structurally similar compounds. The ligand compound was synthesized by the procedure described in the literature. It is noteworthy to mention that 2- (azidomethyl)cyclopropane-1,1-dicarboxylic acid presents the precursor for the synthesis of 2- (aminomethyl)cyclopropane-1,1-dicarboxylic acid, as an example of the constrained γ-amino dicarboxylic acids. The synthesis was achieved by the conversion of the ligand compound into the corresponding sodium dicarboxylate salt and subsequent treatment with [Pd(dien)Cl]Cl (pH maintained between 6-7). The IR and NMR spectra, as well as elemental analysis have confirmed that the Na[Pd(dien)(azmcpda)]. H2O species was formed and that coordination of the ligand compound to the metal ion was established through carboxylate oxygen donor atom.
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Jorgensen, M. J., MJ Rabiet, A. B. Cantor, B. Furie, C. L. Brown, C. B. Shoemaker, and B. C. Furie. "VITAMIN K-DEPENDENT γ-CARBOXYLATION OF FACTOR IX REQUIRES A RECOGNITION SITE CONTAINED WITHIN THE PROPEPTIDE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643564.
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The vitamin K-dependent proteins, including Factor IX (FIX), are calcium-binding proteins that undergo vitamin K-dependent post-translational modification to convert amino terminal glutamic aoid residues to Gla residues. Sequence homology among the propeptides of these proteins suggests a role for this region in designating the adjacent glutamic acid-rich domain for γ-carboxylation during intraoellular processing. Mutations vere made in the propeptide (residues -1 to -18) of FIX, and the effects on γ-carboxylation were assessed. The human FIX cDNA coding sequenoe was modified using oligonucleotide-directed site-specific mutagenesis and was expressed in Chinese hamster ovary cells. The extent of γ-carboxylation of secreted FIX was determined by (1) ability to interact with conformation-specific antibodies directed against the Gla-dependent, metal-stabilized, native structure of FIX, and (2) direct Gla analysis of the alkaline hydrolysate. Using the unmodified coding sequence, 64 ± 17 % of recombinant Factor IX bound to the conformation-specific antibodies, and 9.4 ± 0.7 Gla residues were found (compared with 12 Gla in plasma FIX). When the 18-residue propeptide was deleted, secreted FIX contained no detectable native FIX antigen and no detectable Gla. Similarly, point mutations leading to substitution of Ala for Phe at residue -16 or Glu for Ala at residue -10 led to secretion of FIX containing 2% and 6% native antigen, respectively, and approximately 1-2 Gla residues. The molecular weight of each of the reoombinant FIX species, as estimated by SDS-PAGE, was identical to that of plasma FIX. NH2-terminal sequence analysis of the mutant FIX speoies yielded the NH2-terminal sequence of plasma FIX. These data indicate that the mutations made in the propeptide did not interfere with intracellular proteolytic prooessing of FIX. We conolude that the FIX propeptide participates in defining a recognition site that designates an adjacent glutamic acid-rich domain for γ-carboxylation. The association of the propeptide with the γ-carboxylation recognition site provides the first demonstration of a specific function served by a propeptide in post-translational protein processing.
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Goretzki, L., E. Miller, and A. Henschen. "CLEAVAGE PATHWAY,AND SPECIFICITY OF LEUCOCYTE ELASTASE AS COMPARED TO PLASMIN DURING FIBRINOGEN DEGRADATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643897.
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Plasmin and leucocyte elastase are regarded as the two medically most important fibrin(ogen)-degrading proteolytic enzymes. There is, however, a considerable difference in information available about the cleavage specificities and fragmentation pathways of these two enzymes. Degradation by plasmin has been studied already for a long time in great detail so that now the time course of the degradation, the cleavage sites and the functional properties of many fragments are well known. In contrast, relatively little is known about the degradation by leucocyte elastase, except that the overall cleavage pattern resembles that obtained with plasminIn this investigation the leucocyte elastase-mediated degradation of fibrinogen has been examined by means of proteinchemi-cal methods. Human fibrinogen was incubated with human enzyme material for various periods of time and at some different enzyme concentrations. The split products formed at the various stages were isolated in pure form by gel filtration followed by reversed-phase high-performance liquid chromatography. The fragments were identified by N-terminal amino acid sequence and amino acid composition. The course of the degradation was also monitored by sodium dodecylsulfate-polyacrylamide gel electrophoresis. All cleavage patterns were compared with the corresponding patterns from plasmic degradation. It could be confirmed that X-, D- and E-like fragments are formed also with elastase. However, several early elastolytic Aα-chain fragments are characteristically different from plasmic fragments. The previously identified N-terminal cleavage site in the Aα-chain, i.e. after position 21, was found to be the most important site in this region of fibrinogen. The very early degradation of the Aα-chain N-terminus by elastase is in strong contrast to the stability against plasmin. Several cleavage sites in N-terminal region of the Bβ-chain were observed, though the low amino acid specificity of elastase partly hampered the identification. The γ-chain N-terminus was found to be as highly stable towards elastase as towards plasmin. The results are expected to contribute to the understanding of the role of leucocyte elastase in pathophysiologic fibrino(geno)lysis
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Suttie, W. J., A. Cheung, and M. G. Wood. "ENZYMOLOGY OF THE VITAMIN K-DEPENDENT CARBOXYLASE: CURRENT STATUS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643991.
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The vitamin K-dependent microsomal carboxylase converts glutamyl residues in precursor proteins to γ-carboxyglutamyl (Gla) residues in completed proteins. The enzyme activity is present in significant activities in most non-skeletal tissues but has been studied most extensively in rat and bovine liver. Early studies of the enzyme utilized bound precursors of vitamin K-dependent clotting factors as substrates for the enzyme and demonstrated that the enzyme requires the reduced form of vitamin K (vitamin KH2), O2, and CO2. Subsequent investigations have taken advantage of the observation that the enzyme will carboxylate low-molecular-weight peptide substrates with Glu-Glu sequences. Utilizing a substrate such as Phe-Leu-Glu-Glu-Leu, it has been possible to demonstrate that γ-C-H release from the Glu residue of a substrate is independent of CO2 concentration. The formation of vitamin K 2,3-epoxide can also be demonstrated in a crude microsomal system, and it can be shown that the formation of this metabolite can be stimulated by the presence of a peptide substrate of the carboxylase. These observations have led to the general hypothesis that the mechanism of action of the enzyme involves interaction of vitamin KH2 with O2 to form an oxygenated intermediate that can interact with a substrate Glu residue to abstract a γ-hydrogen and in the process he converted to vitamin K epoxide (KO). The current evidence suggests that, either directly or indirectly, removal of the γ-C-H results in the formation of a carbanion at the γ-position of the Glu residue which can interact with CO2 to form Gla. The Glu residue intermediate which is formed can be demonstrated to partition between accepting a proton in the media to reform Glu, or interacting with CO2 to form Gla. Current data do not distinguish between the direct formation of a carbanion coupled to proton removal, or the participation of a reduced intermediate. Recent studies have demonstrated that the enzyme will carry out a partial reaction, the formation of vitamin K epoxide, at a decreased rate in the absence of a Glu site substrate. Epoxide formation under these conditions has the same for O2 as the carboxylation reaction and is inhibited in the same manner as the carboxylation reaction. In the presence of saturating concentrations of a Glu site substrate and C02, the ratio of KO formed, γ-C-H released, and C02 formed is 1:1:1. However, KO formation can be uncoupled from and proceeds at a higher rate than γ-C-H bond cleavage and Gla formation at low Glu site substrate concentrations. At saturating concentrations of CO2, Gla formation is equivalent to γ-C-H bond cleavage, and this unity is not altered by variations in vitamin KH2 or peptide substrate concentrations. Natural compounds with vitamin K activity are 2-Me-l,4-naphthoquinones with a polyprenyl side chain at the 3-position. Studies of vitamin K analogs have demonstrated that a 2-Me group is essential for activity but that the group at the 3-position can vary significantly. Modification of the aromatic ring of the naphthoquinone nucleus by methyl group substitution can result in alterations of either the rate of the carboxylation reaction or the apparent affinity of the enzyme for the vitamin. Studies of a large number of peptide substrates have failed to reveal any unique primary amino acid sequence which is a signal for carboxylation. However, current evidence from a number of sources suggests that a basic amino acid rich "propeptide" region of the intracellular form of the vitamin K-dependent proteins is an essential recognition site for the enzyme. This region of the precursor is lost in subsequent processing, and the manner in which it directs this posttranslational event is not yet clarified. Supported by NIH grant AM-14881.