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Academic literature on the topic 'Peptidases – Synthèse'
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Journal articles on the topic "Peptidases – Synthèse"
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LE FLOC’H, N., and B. SEVE. "Le devenir des protéines et des acides aminés dans l’intestin du porc : de la digestion à l’apparition dans la veine porte." INRAE Productions Animales 13, no. 5 (October 22, 2000): 303–14. http://dx.doi.org/10.20870/productions-animales.2000.13.5.3798.
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La digestion intestinale des protéines alimentaires fait intervenir des protéases d’origine pancréatique et des peptidases intestinales. Les produits de la digestion sont constitués d’acides aminés libres et de peptides relativement abondants. Acides aminés et peptides sont transportés dans l’entérocyte où ces derniers subissent une hydrolyse. Les acides aminés libres présents dans la veine porte présentent un profil bien différent de celui des protéines alimentaires. En effet, le métabolisme intestinal des acides aminés est très actif. Afin d’assurer la synthèse des protéines constitutives et sécrétées, l’intestin prélève des acides aminés à la fois dans la lumière intestinale et dans le sang artériel. Cet organe renouvelle plus de 50 % de ses protéines par jour et la synthèse de protéines bien particulières comme les mucines engendre des besoins élevés en certains acides aminés comme la thréonine. L’intestin est le principal tissu utilisant la glutamine artérielle et le glutamate alimentaire. Le catabolisme intestinal de ces acides aminés produit de l’alanine, de l’acide aspartique, de la proline et, par l’intermédiaire des enzymes du cycle de l’urée, de l’ornithine, de la citrulline et de l’arginine. Les acides aminés indispensables n’échapperaient pas non plus au catabolisme intestinal. Le rôle de l’intestin ne se limite donc pas à la digestion des protéines et à l’absorption des acides aminés. Son métabolisme modifie profondément la disponibilité des acides aminés alimentaires pour le reste de l’organisme.
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Dubois, Damien, Olivier Baron, Antony Cougnoux, Julien Delmas, Nathalie Pradel, Michèle Boury, Bernadette Bouchon, et al. "ClbP Is a Prototype of a Peptidase Subgroup Involved in Biosynthesis of Nonribosomal Peptides." Journal of Biological Chemistry 286, no. 41 (July 27, 2011): 35562–70. http://dx.doi.org/10.1074/jbc.m111.221960.
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The pks genomic island of Escherichia coli encodes polyketide (PK) and nonribosomal peptide (NRP) synthases that allow assembly of a putative hybrid PK-NRP compound named colibactin that induces DNA double-strand breaks in eukaryotic cells. The pks-encoded machinery harbors an atypical essential protein, ClbP. ClbP crystal structure and mutagenesis experiments revealed a serine-active site and original structural features compatible with peptidase activity, which was detected by biochemical assays. Ten ClbP homologs were identified in silico in NRP genomic islands of closely and distantly related bacterial species. All tested ClbP homologs were able to complement a clbP-deficient E. coli mutant. ClbP is therefore a prototype of a new subfamily of extracytoplasmic peptidases probably involved in the maturation of NRP compounds. Such peptidases will be powerful tools for the manipulation of NRP biosynthetic pathways.
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Gaikwad, Bhaskar G., and Kritika R. Dwivedy. "Study of Glycogen Synthase and Amino Peptidase." Research Journal of Science and Technology 8, no. 1 (2016): 51. http://dx.doi.org/10.5958/2349-2988.2016.00007.3.
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Kumar, Davinder, Virender Kumar, Rakesh Marwaha, and Gajendra Singh. "Oxadiazole-An Important Bioactive Scaffold for Drug Discovery and Development Process Against HIV and Cancer- A Review." Current Bioactive Compounds 15, no. 3 (May 7, 2019): 271–79. http://dx.doi.org/10.2174/1573407213666171017160359.
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Background: Acquired immunodeficiency syndrome (AIDS) and cancer treatment have been a major task for research scientists and pharmaceutical industry for the last many years. Seeking to the development, many promising chemical entities especially five-membered heterocyclic rings like oxadiazole have revealed good anticancer and anti HIV activities. The current review enlists some recently developed anti-HIV and anti-cancer oxadiazole moieties. Methods: on the basis of structural modification for the syntheses of new oxadiazole analogs, the new anti-HIV and anti-cancer agents have been summarized, which can improve treatment of AIDs and cancer. Results: The oxadiazole ring is more potent in comparison to some other heterocyclic rings (five and six membered) towards anti-HIV and anti-cancer activities. The important mechanisms involved for anti HIV and anticancer activity are mainly inhibition of enzymes like protease, HIV-integrase, telomerase, histone deacetylase, methionine amino peptidase, thymidylate synthase and focal adhesion kinase and inhibition of some growth factors. Conclusion: By reviving the past literature about 50 most potent oxadiazole derivatives, depending upon activity and structural modifications, have been selected as potent anti-HIV, and anti-cancer agents. Thus, oxadiazole seems to be a ‘privileged structure’ for further screening and syntheses of the new drug analogs against life threatening HIV and cancer like diseases.
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Ajmer Singh Grewal, Neelam Sharma, Sukhbir Singh, and Sandeep Arora. "Molecular Docking Studies of Phenolic Compounds from Syzygium cumini with Multiple Targets of Type 2 Diabetes." Journal of Pharmaceutical Technology, Research and Management 6, no. 2 (November 2, 2018): 125–33. http://dx.doi.org/10.15415/jptrm.2018.62009.
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Treatment of type 2 diabetes without any side effects is still a challenge to the medical system. This leads to increasing demand for natural products with antidiabetic activity with fewer side effects. Syzygium cumini is a traditional herbal medicinal plant and is reported to possess a variety of pharmacological actions. It contains various types of chemical constituents including terpenoids, tannins, anthocyanins, flavonoids and other phenolic compounds. Some flavonoids and other phenolic compounds from S. cumini were reported in literature to have type 2 antidiabetic potential. The main objective of the current investigation was in silico screening of some phenolic compounds from S. cumini against multiple targets associated with type 2 diabetes to explore the mechanism of antidiabetic action and prediction of binding mode using molecular docking studies. In silico docking studies were performed for the selected molecules in the binding site of multiple targets associated with type 2 diabetes (α-glucosidas , dipeptidyl peptidase 4, glycogen synthase kinase 3, glucokinase and glucagon receptor). Amongst the compounds tested in silico, rutin showed appreciable binding with multiple targets of type 2 diabetes including α-glucosidase, dipeptidyl peptidase 4, glycogen synthase kinase 3, and glucagon receptor. Catechin was found to inhibit both α-glucosidase, and dipeptidyl peptidase 4. This information can be utilized for the design and development of potent multi-functional candidate drugs with minimal side effects for type 2 diabetes therapeuticsa.
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Domínguez-Vías, Germán, Ana Belén Segarra, Manuel Ramírez-Sánchez, and Isabel Prieto. "The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats." Nutrients 12, no. 3 (February 28, 2020): 636. http://dx.doi.org/10.3390/nu12030636.
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High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.
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Osman, Christof, Claudia Wilmes, Takashi Tatsuta, and Thomas Langer. "Prohibitins Interact Genetically with Atp23, a Novel Processing Peptidase and Chaperone for the F1FO-ATP Synthase." Molecular Biology of the Cell 18, no. 2 (February 2007): 627–35. http://dx.doi.org/10.1091/mbc.e06-09-0839.
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The generation of cellular energy depends on the coordinated assembly of nuclear and mitochondrial-encoded proteins into multisubunit respiratory chain complexes in the inner membrane of mitochondria. Here, we describe the identification of a conserved metallopeptidase present in the intermembrane space, termed Atp23, which exerts dual activities during the biogenesis of the F1FO-ATP synthase. On one hand, Atp23 serves as a processing peptidase and mediates the maturation of the mitochondrial-encoded FO-subunit Atp6 after its insertion into the inner membrane. On the other hand and independent of its proteolytic activity, Atp23 promotes the association of mature Atp6 with Atp9 oligomers. This assembly step is thus under the control of two substrate-specific chaperones, Atp10 and Atp23, which act on opposite sides of the inner membrane. Strikingly, both ATP10 and ATP23 were found to genetically interact with prohibitins, which build up large, ring-like assemblies with a proposed scaffolding function in the inner membrane. Our results therefore characterize not only a novel processing peptidase with chaperone activity in the mitochondrial intermembrane space but also link the function of prohibitins to the F1FO-ATP synthase complex.
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Wang, Han, Qingchun Zhou, Jason W. Kesinger, Chad Norris, and Cammi Valdez. "Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish." Experimental Biology and Medicine 232, no. 9 (October 2007): 1170–80. http://dx.doi.org/10.3181/0703-rm-77.
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We previously determined that yquem harbors a mutation in the gene encoding uroporphyrinogen decarboxylase (UROD), the fifth enzyme in heme biosynthesis, and established zebrafish yquem ( yqe tp61) as a vertebrate model for human hepatoery-thropoietic porphyria (HEP). Here we report that six exocrine peptidase precursor genes, carboxypeptidase A, trypsin precursor, trypsin like, chymotrypsinogen B1, chymotrypsinogen 1-like, and elastase 2 like, are downregulated in yquem/urod (−/−), identified initially by microarray analysis of yquem/urod zebrafish and, subsequently, confirmed by in situ hybridization. We then determined downregulation of these six zymogens specifically in the exocrine pancreas of sauternes ( sau tb223) larvae, carrying a mutation in the gene encoding δ-amino-levulinate synthase (ALAS2), the first enzyme in heme biosynthesis. We also found that ptf1a, a transcription factor regulating exocrine zymogens, is downregulated in both yquem/urod (−/−) and sau/alas2 (−/−) larvae. Further, hemin treatment rescues expression of ptf1a and these six zymogens in both yquem/urod (−/−) and sauternes/alas2 (−/−) larvae. Thus, it appears that heme deficiency downregulates ptf1a, which, in turn, leads to downregulation of exocrine zymogens. Our findings provide a better understanding of heme deficiency pathogenesis and enhance our ability to diagnose and treat patients with porphyria or pancreatic diseases.
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Zhou, Suping, Roger J. Sauvé, Zong Liu, Sasikiran Reddy, Sarabjit Bhatti, Simon D. Hucko, Yang Yong, Tara Fish, and Theodore W. Thannhauser. "Heat-induced Proteome Changes in Tomato Leaves." Journal of the American Society for Horticultural Science 136, no. 3 (May 2011): 219–26. http://dx.doi.org/10.21273/jashs.136.3.219.
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Three tomato (Solanum lycopersicum) cultivars [Walter LA3465 (heat-tolerant), Edkawi LA 2711 (unknown heat tolerance, salt-tolerant), and LA1310 (cherry tomato)] were compared for changes in leaf proteomes after heat treatment. Seedlings with four fully expanded leaves were subjected to heat treatment of 39/25 °C at a 16:8 h light–dark cycle for 7 days. Leaves were collected at 1200 hr, 4 h after the light cycle started. For ‘Walter’ LA3465, heat-suppressed proteins were geranylgeranyl reductase, ferredoxin-NADP (+) reductase, Rubisco activase, transketolase, phosphoglycerate kinase precursor, fructose–bisphosphate aldolase, glyoxisomal malate dehydrogenase, catalase, S-adenosyl-L-homocysteine hydrolase, and methionine synthase. Two enzymes were induced, cytosolic NADP-malic enzyme and superoxide dismutase. For ‘Edkawi’ LA2711, nine enzymes were suppressed: ferredoxin-NADP (+) reductase, Rubisco activase, S-adenosylmethionine synthetase, methioine synthase, glyoxisomal malate dehydrogenase, enolase, flavonol synthase, M1 family peptidase, and dihydrolipoamide dehydrogenase. Heat-induced proteins were cyclophilin, fructose-1,6-bisphosphate aldolase, transketolase, phosphoglycolate phosphatase, ATPase, photosystem II oxygen-evolving complex 23, and NAD-dependent epimerase/dehydratase. For cherry tomato LA1310, heat-suppressed proteins were aminotransferase, S-adenosyl-L-homocysteine hydrolase, L-ascorbate peroxidase, lactoylglutathione lyase, and Rubisco activase. Heat-induced enzymes were glyoxisomal malate dehydrogenase, phosphoribulokinasee, and ATP synthase. This research resulted in the identification of proteins that were induced/repressed in all tomato cultivars evaluated (e.g., Rubisco activase, methionine synthase, adenosyl-L-homocysteine hydrolase, and others) and those differentially expressed (e.g., transketolase).
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Dzikaite, Vijole, Arvydas Kanopka, Jeremy H. Brock, Arunas Kazlauskas, and Öjar Melefors. "A novel endoproteolytic processing activity in mitochondria of erythroid cells and the role in heme synthesis." Blood 96, no. 2 (July 15, 2000): 740–46. http://dx.doi.org/10.1182/blood.v96.2.740.
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Abstract The erythroid isoform of aminolevulinate synthase (eALAS) protein is a major control point in erythroid heme synthesis and hemoglobin formation. Erythroid cells were extracted from mouse blood and bone marrow and metabolically labeled with 35S-methionine. This was followed by immunoprecipitation of eALAS protein products. The results show that the N-terminus of the expected full-length 59-kd form of the eALAS protein is truncated in bone marrow erythroid cells by approximately 7 kd. More differentiated erythroid cells in the peripheral blood exhibit very little of this protein truncation. Erythroid cells from the bone marrow were isolated using monoclonal antibody TER-119 and were shown to contain a unique endoprotease activity that could cleave the eALAS protein to the shorter form in vitro. With or without the mitochondrial signal sequence, the eALAS protein could serve as a substrate for the cleavage. This cleavage renders a functional eALAS protein and only removes a domain of unclear function, which has previously been reported to vary in size as a result of alternative RNA splicing. The protease activity was enriched from the membranes of mitochondria from bone marrow cells and was shown to be different from mitochondrial processing peptidase, medullasin, and other known proteases. Apart from the mitochondrial processing peptidase that cleaves the import signal sequence, this is the first description of a mitochondrially located site-specific processing protease activity.
Dissertations / Theses on the topic "Peptidases – Synthèse"
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Gaucher, Bérangère. "Prodrogues d'inhibiteurs de la protéase du virus de l'immunodéficience humaine (VIH) : synthèse et évaluation de leurs propriétés pharmacologiques." Nice, 2002. http://www.theses.fr/2002NICE5717.
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Rocheblave, Luc. "Conception, synthèse et évaluation antivirale de nouveaux dérivés pseudopeptidiques, inhibiteurs de la protéase du VIH-1, contenant le motif (2-phenylsulfanyl-1-hydroxyethyl) sulfonamide." Aix-Marseille 2, 2000. http://www.theses.fr/2000AIX22079.
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Charbonnier-Gérardin, Christine. "Nouvelles applications en synthèse des acides 2-dialkylphosphonoalcanoique : préparation de phosphonopeptides inhibiteurs de peptidases." Nancy 1, 1991. http://www.theses.fr/1991NAN10063.
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Une conception générale de synthèse de phosphonopeptides renfermant un motif phosphore du cote c-terminal ou du cote n-terminal est proposée à partir d'un même substrat acide 2-dialkylphosphonoalcanoique. L'objectif est de préparer des inhibiteurs de peptidases présentant une activité thérapeutique. L'approche la plus efficace pour introduire le motif phosphonate sous forme enantiomeriquement pure dans les phosphonopeptides n-terminaux consiste à utiliser la chaine peptidique chirale pour induire une asymétrie sur le carbone directement lié au phosphore. Le couplage peptidique a également été mis au point entre l'acide phosphonoacetique et l'acide 6-aminopenicillanique dans le but de préparer de nouveaux antibiotiques. L'étude du comportement des phosphonopeptides n-terminaux en tant que réactifs de Honer a été abordée pour préparer des peptides insaturés, substituts possibles de peptides à usage thérapeutique. Enfin, la réactivité de thiols sur les chlorures d'acides 2-dialkylphosphonoalcanoiques constitue une voie de synthèse de dialcoxyphosphorylalcane thioates de s-alkyle, qui conduisent eux-mêmes par réaction de Horner à des thioesters éthyléniques, cette réaction des généralisable aux dérivés chrysanthemiques
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Rolland, Valérie. "Synthèse peptidique en milieu organique par une endoprotéase modifiée et supportée." Montpellier 2, 1990. http://www.theses.fr/1990MON20113.
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Ce travail a pour but d'elaborer une methodologie originale permettant d'acceder au couplage de fragments peptidiques en eliminant tout risque de racemisation et la protection des chaines laterales des acides amines. Dans une premiere partie l'alpha-chymotrypsine endoprotease specifique vis-a-vis des acides amines aromatiques, est modifiee par des fonctions acryliques et copolymerisee avec des agents de reticulation et de maille a base de polyethylene glycols eux aussi fonctionnalises. Dans une deuxieme partie nous avons etudie les capacites de ce biocatalyseur supporte dans des couplages peptidiques en milieu organiques ou les phenomenes d'hydrolyse secondaire, constates dans la synthese enzymatique en milieu aqueux, sont quasiment elimines. Le biocatalyseur supporte permet l'obtention de produits optiquement purs avec des rendements tres satisfaisants. L'interet economique et industriel d'un tel catalyseur est son recyclage: il peut catalyser plusieurs cycles de reactions sans perdre son activite
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Elhilali, Abdellah. "Synthèse et cyclisation de tétra N-hydroxy peptides." Montpellier 2, 1992. http://www.theses.fr/1992MON20144.
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Les recherches effectuees sont centrees sur la synthese de tetra n-hydroxypeptides, incluant la n-hydroxyphenylalanine en vue de leur cyclisation. L'oxydation de la base de schiff de l'ester methylique de la phenylalanine par le mmpp, suivi de l'ouverture de l'oxaziridine conduit au phe(n-oh)ome. Deux types de n-hydroxypeptides sont obtenus: 1) les peptides possedant une liaison n-hydroxyamide dont la formation est etudiee. Le reactif retenu pour les couplages est de dppcl; 2) les peptides possedant la substitution oh sur l'azote terminal qui sont synthetises en presence de dcc/hobt. La deprotection des peptides n-proteges est discutee et les conditions sont etudiees pour eviter le clivage de la liaison n-oh. L'introduction du n-oh permet la cyclisation du tetrapeptide phe-phe(n-oh)-phe-phe par le dppa en cyclotetrapeptide
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Richard, Jean-Alexandre. "Synthèse de sondes luminescentes utilisant un bras réactif auto-immolable : application à la détection de peptidases." Thesis, Rouen, INSA, 2008. http://www.theses.fr/2008ISAM0011.
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L’imagerie optique est actuellement en train de révolutionner le diagnostic pré-clinique et le développement des médicaments. Dans ce contexte, la société QUIDD développe des sondes intelligentes capables de mettre en évidence des processus biologiques impliqués dans les maladies. Ainsi, cette thèse a pour objectif le développement d’une méthode générale pour la synthèse de sondes luminescentes visant la détection de peptidases. Pour cela, des sondes composées d’un substrat peptidique et d’une espèce luminescente phénolique reliés entre eux par un bras réactif auto-immolables ont été développées. Deux approches ont été envisagées : une stratégie utilisant des pro-fluorophores à phénol dont l’émission de fluorescence est éteinte lorsque leur fonction phénol est substituée. Une autre stratégie a consisté en l’utilisation de 1,2-dioxétanes dont la libération dans le milieu engendre une émission spontanée de lumière. Cette thèse présente tout d’abord la validation de cette stratégie, notamment pour la détection de la caspase-3, une enzyme fortement impliquée dans le processus apoptotique. La deuxième partie de ce travail relate les efforts effectués afin de permettre l’utilisation de ces sondes en imagerie in vivoOptical imaging is currently revolutionizing pre-clinic diagnosis and drug development. In that context, QUIDD develops smart probes able to follow biological events involved in biological disorders. The aim of this PhD work was to provide a general method for the synthesis of luminescent probes able to detect proteases. For that purpose, probes composed of a peptide substrate and a phenolic luminescent moiety connected by a self-immolative linker were developed. Two strategies were investigated: a first strategy involved phenolic pro-fluorophores, whose fluorescence is quenched when their phenol functionality is substituted. A second strategy took advantage of 1,2-dioxetanes whose liberation in the medium results in a spontaneous light emission. The first objective of this work was to provide a proof of concept of these strategies, especially for the detection of caspase-3, a key enzyme involved in the apoptotic process. The second part of this work was devoted to the extension of the strategy to in vivo imaging
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Bouifraden, Samira. "Synthèses stéréosélectives de glycosyl-alpha-aminoesters et de glycopeptides dérivés." Montpellier 2, 1996. http://www.theses.fr/1996MON20228.
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Le travail que nous decrivons avait pour but de developper de nouvelles syntheses de glycosyl-aminoacides et glycopeptides derives dans lesquels le sucre et l'aminoacide sont lies par une liaison carbone-carbone. Nous avons mis au point une condensation de differents enolates de glycine sur le carbonyle en position 3 de l' -d-ribohexofuranos-3-ulose convenablement protege. La diastereoselectivite de ces reactions est dans l'ensemble assez remarquable. Elle implique une double induction asymetrique et depend a la fois des groupements de la fonction ester et de la nature des groupements protecteurs de la fonction amine. Apres deprotection selective des fonctions amine ou acide, ces composes ont pu etre couples avec d'autres aminoacides pour donner les glycopeptides attendus
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Drouot, Cyrille. "Synthèse combinatoire de pseudopeptides inhibiteurs de l'activité "Bêta" sécrétase impliquée dans la maladie d'Alzheimer. Synthèse en phase solide du peptide amyloi͏̈de 1-42 et d'analogues du peptide intestinal vasoactif." Montpellier 2, 1998. http://www.theses.fr/1998MON20142.
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Ce travail se situe a l'interface de la chimie et de la biologie. La chimie peptidique et pseudopeptidique a comme principal objectif la synthese d'outils pharmacologiques indispensables a la comprehension des phenomenes cellulaires complexes. Au cours de ce travail nous avons aborde, la synthese d'inhibiteurs necessaires pour la caracterisation d'une activite enzymatique, et la synthese d'analogues peptidiques afin de decrire les relations structure fonction d'un peptide et de son recepteur. Le depot amyloide de peptide a est sans doute l'evenement central qui rend compte de l'etiologie de la maladie d'alzheimer. La synthese d'inhibiteurs d'une des activites enzymatiques impliquee dans la liberation de ce peptide a ete l'objectif de ce travail. Cette activite appelee secretase pourrait appartenir a la famille des protease acide ou des metalloproteases. L'utilisation de la chimie combinatoire a conduit a la synthese d'une librairie pseudopeptidiques incorporant un motif chimique specifique des proteases acides. Les resultats biologiques obtenus nous ont conduit ensuite a la synthese de pseudopeptides inhibiteurs d'enzymes de type metalloprotease. D'autre part la synthese de ce peptide a long de 42 amino acides a ete effectuee en phase solide. Cette strategie est rapide et efficace et permet d'obtenir le produit final avec une purete satisfaisante. La derniere partie de ce travail concerne la synthese d'analogues du peptide intestinal vasoactif. L'incorporation d'une alanine sur chacune des 28 positions des acides amines constitutifs du vip, nous a permis d'obtenir des informations sur la relation structure fonction de ce peptide vis a vis de ses deux sous-types de recepteurs.
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Yaouancq, Loïc. "Méthodologie de synthèse et applications des glycines α-hétérosubstituées." Paris 5, 2002. http://www.theses.fr/2002PA05P602.
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Ce manuscrit décrit, dans sa 1ère partie, la méthodologie de synthèse des α-alkylamino glycines orthogonalement protégées au niveau de deux amines. La méthode mise au point permet en deux étapes seulement d 'obtenir ces analogues d acides aminés directement utilisables en synthèse peptidique. Avec cette méthode un grand nombre d' analogue d' acides minés a été synthétisé, seuls les analogues de la cystéine et de l' aspartate étant non synthétisable car intrinsèquement instable. Nous avons testé ces pseudo peptides en synthèse peptidique en stratégie Cbz- / Boc-. Malheureusement , la déprotection des groupes Boc- entraîne la dégradation des produits déprotégé à cause de la fra gilité de la liaison carbone α-azote dans des conditions acides. Néanmoins cela démontre la possibilité d utiliser ces glycines α-aminosubstituées en synthèse peptidique. Dans la seconde partie du manuscrit les synthèses d' un substrat chrom ogène et de trois substrats suicides, inhibiteurs irréversibles de l' enzyme VanX sont décritsThis thesis described in the first part. The methodology for the synthesis of the orthogonally protected α-alkylamino glycines. The method developed in our laboratory permit to obtain in two steps theses aminoacids analogs directly usable in peptide synthesis. With this method a large quantity of analogs has been synthesized, only the analogs of cystein and aspartate are not synthesisable due to their intrinsic instability. We have tested different aminoacid analogues in peptide synthesis in Cbz-/Boc- strategy. Unfortunately, the deprotection of the Boc- group is not possible without degradation of the unprotected product due to labile carbon α-nitrogen bond under acidic condition used for the deprotection. Nevertheless, it demonstrates the capability to use theses orthogonally protected a-amino substituted glycines in peptide synthesis. The second part of the PhD concern the design and the synthesis of one new chromogenic substrate and three mechanismbased inhibitor of the D-Analyl-D-Alanine aminopeptidase (VanX)
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Bore, Christian. "Utilisation d'ammonia-lyases de "Rhodotorula glutinis" et "Escherichia coli" pour la synthèse d'acides aminés non-naturels et exotiques." Montpellier 2, 1991. http://www.theses.fr/1991MON20220.
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La synthese d'acides l amines aromatiques proteiques ou non-proteiques par la phenylalanine ammonia-lyase de rhodotorula glutinis a ete realisee par addition d'ammoniaque sur des derives et des analogues de l'acide trans cinnamique. Dans un premier temps le milieu de culture pour l'obtention d'une activite enzymatique maximale a ete realisee par l'utilisation de peptone de caseine. Dans un deuxieme temps differents acides amines aromatiques ou pseudo-aromatiques ont ete prepares. D'autre part l'utilisation de l'aspartate ammonia-lyase d'escherichia coli a permis de synthetiser quelques acides l amines non naturels a chaines alkyles. Ainsi une nouvelle voie de synthese de la l norvaline a pu etre realisee