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FONTANA, DILETTA. « Characterization of the role of mutated ETNK1 in the onset of atypical Chronic Myeloid Leukemia ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241117.
Texte intégralRésumé :
La leucemia mieloide cronica atipica (aCML) è un disordine clonale appartenente al gruppo delle sindromi mielodisplastiche/mieloproliferative (MDS/MPN). Circa il 13% dei casi di aCML è caratterizzato dalla presenza di mutazioni somatiche a carico del gene ETNK1, codificanti per le sostituzioni amminoacidiche H243Y, N244S e G245V. Precedentemente, abbiamo dimostrato che sia in campioni primari di aCML ETNK1-positiva sia nella linea cellulare TF1 trasdotta con ETNK1 mutato, le mutazioni causano una diminuzione dell’attività enzimatica di ETNK1, causando una riduzione nei livelli intracellulari di fosfoetanolamina (P-Et). Per caratterizzare il ruolo funzionale delle mutazioni di ETNK1, ho creato un nuovo modello cellulare isogenico CRISPR/Cas9 nel quale la mutazione N244S è presente come variante in eterozigosi, e ho studiato l’effetto funzionale della modulazione di P-Et applicando diverse strategie, tra cui approcci di metabolimica, lipidomica, analisi di espressione genica, ed esperimenti di respirazione mitocondriale, dimostrando che la mutazione di ETNK1 (i) causa un aumento del potenziale di membrana mitocondriale, (ii) un cambiamento della morfologia mitocondriale, (iii) un aumento della produzione di ROS, (iv) e aumenta il tasso di mutazioni al DNA genomico. Inoltre, ho dimostrato che l’aumentata attività mitocondriale causata dalla mutazione di ETNK1 è dovuta a una diretta competizione tra P-Et e succinato per l’enzima succinato deidrogenasi (complesso II). Infine, esperimenti di ricostruzione della gerarchia clonale delle mutazioni somatiche nei pazienti affetti da aCML indicano che le mutazioni di ETNK1 sono eventi precoci nel processo evolutivo della patologia, suggerendo per ETNK1 un ruolo di induttore di un fenotipo mutante, il quale a sua volta contribuisce all’accumulo di ulteriori mutazioni oncogeniche.Atypical chronic myeloid leukemia (aCML) is a clonal disorder belonging to the MDS/MPN syndromes. About 13% of aCML cases carry somatic mutations in ETNK1 gene, encoding for H243Y, N244S and G245V substitutions. We previously showed that, in both ETNK1-positive aCML primary samples and TF1 cells transduced with mutated ETNK1, the mutations lead to an impairment of ETNK1 enzymatic activity, responsible for a decrease in the intracellular level of phosphoethanolamine (P-Et). To dissect the functional role of ETNK1 mutations I created a new isogenic CRISPR/Cas9 cellular model in which ETNK1 N244S mutation was present as heterozygous variant, and I investigated the functional effect of P-Et modulation by a combined approach involving metabolomics, lipidomics, whole-transcriptome sequencing, ChIP and mitochondria respiration analyses, showing that it causes (i) increased mitochondria potential, (ii) change in mitochondria morphology, (iii) increased ROS production, (iv) increased gDNA mutation rate. I also showed that the increased mitochondrial activity in presence of ETNK1 mutations is caused by a direct competition between P-Et and succinate for complex II succinate dehydrogenase enzyme. Finally, experiments focused on the reconstruction of the hierarchy of somatic mutations in aCML patients showed that ETNK1 somatic mutations are early events in the subclonal history of aCML, which fits with a role of ETNK1 as an inducer of a mutant phenotype, which in turn would accelerate the accumulation of further oncogenic mutations.
2
KHANDELWAL, PRAVEEN. « Elucidating the oncogenic role of genetic events in BCR-ABL1 positive chronic myeloid leukemia ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2016. http://hdl.handle.net/10281/99449.
Texte intégralRésumé :
In hematological myeloid malignancies the accumulation of oncogenic events plays a significant role in disease progression. Therefore, in this work, we studied (i) the mutational landscape in typical chronic myeloid leukemia (CML) patients and (ii) the neoplastic role of Setbp1 mutation in atypical chronic myeloid leukemia (aCML).
1) We evaluated somatic variants in CML patients by Next Generation Sequencing, to study the molecular pathogenesis of cancer. We conducted a mutational analysis on 23 chronic phase BCR-ABL1+ CML patients through exome and RNA sequencing performed on diagnosis samples. A total of 107 non-synonymous variants (range 0-11 per patient) were identified by setting a threshold of mutation frequency >25%, which corresponds to the presence of a heterozygous mutation in >50% of cells, assuming a pure tumoral sample. A positive correlation was observed between number of mutations and patient age, indicating that several events were passenger mutations, being immortalized by the neoplastic transformation. However, when using a newly in-house developed tool (Oncoscore) to weigh the oncogenic potential of each mutation, a significant correlation was observed between the Sokal score and Oncoscore by using linear model statistical analysis. In long term follow-up (>2 years), 21 CML patients achieved complete cytogenetic responses (CCyR) and 2 failed to achieve any cytogenetic response with tyrosine kinase inhibitors. These two patients showed an Oncoscore value of (165.4 ±27.2) which was significantly higher than the one (80.6 ±12.7) in the 21 responding patients. No fusions (other than BCR/ABL1) were identified by RNA Seq, and no chromosomal alterations were observed by using the CEQer software. In conclusion, CML patients at diagnosis carry genetic alterations additional to the BCR/ABL1 fusion, which could be relevant for response to treatment and progression of the disease.
2) We aimed to gain insights into the biological role of Setbp1 mutations found in aCML patients, by invivo genetic manipulation techniques. Recently, by NGS approach, we identified a recurrent SETBP1 missense mutation in aCML patients, associated with poor overall survival. The most frequent SETBP1 mutations identified in various MDS/MPN neoplasms were positioned at D868N, S869G, G870S and I871T. The same mutations identified in myeloid malignancies had previously been observed as de novo recurrent germline mutations responsible for Schinzel-Giedion syndrome. Unfortunately, the biological role of Setbp1 and its activity in leukemic transformation is not exactly known. Therefore, an improved understanding of the molecular mechanism is imperative. So, we applied genetic engineering to construct a conditional knock-in model for dissecting the role of leukemia transforming factors in heterozygous Setbp1G870S mice. For construction, 3 genomic fragments of Setbp1 intron 3 and exons 4 through 6 were subcloned into the conditional replacement vector pDELBOY-3X. The linearised vector was then transfected into murine ES cells. We are currently screening ES cells to identify a correctly targeted clone for blastocyst injection and transplantion into pseudo-pregnant mice. The 1st generation Setbp1WT/floxed mice will express wild type Setbp1 under the control of its endogenous promoter. Thereafter, the expression of Setbp1G870S would be induced in a conditional manner with Cre-mediated recombination. Depending on the type of promoter driving Cre recombinase expression, the mutant allele will be expressed either constitutively (germline) or somatically, and it will be possible to study the oncogenic effects of Setbp1G870S in specific tissues, or in all tissue/cells. Additionally, the molecular interactions and physiological pathways accountable for tumorigenesis and the clonal evolution pattern will be examined by implementing the molecular and functional genomic techniques, which help in better understanding of developing targeted therapies.
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PERONACI, MARCO. « Characterization of new oncogenes identified through NGS-based analysis of leukemias : SETBP1 and ETS2-ERG ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/144663.
Texte intégralRésumé :
In the past years, the improvements in sequencing technology led to the development of “Next Generation Sequencing” (NGS) technologies. Several NGS approaches exist. Whole genome sequencing (WGS) and whole exome sequencing (WES) allow the identification of genomic alterations such as small insertions/deletions, point mutations and structural variants. Whole transcriptome sequencing (RNA-Seq) permits to quantify gene expression profiles and to detect alternative splicing and fusion transcripts. Recently, by using WES on atypical chronic myeloid leukemia (aCML) samples, our group identified recurrent mutations in SETBP1 gene; also, by using RNA-Seq on acute myeloid leukemia (AML), we identified a new fusion gene: ETS2-ERG. In aCML, SETBP1 mutations disrupt a degron binding site, leading to a decreased protein degradation. This leads to an increased amount of SETBP1 protein interacting with its natural ligand SET, which in turn acts inhibiting the protein phosphatase 2A (PP2A) oncosuppressor. Interestingly, the SETBP1 mutational cluster affected in aCML is highly conserved and the same mutations were also observed in the Schinzel-Giedion syndrome (SGS). However, the inhibition of the PP2A by SET, the only known interactor of SETBP1, does not explain the phenotype of SGS. To further characterize the role of SETBP1 protein, 293 Flp-In isogenic cellular models expressing the empty vector or the wild type (WT) or mutated (G870S) form of SETBP1 were established. In these models SETBP1 was fused with a V5 tag. Chromatin Immunoprecipitation sequencing experiments (Chip-Seq) performed against V5 confirmed the binding of SETBP1 to DNA, both for the WT and G870S forms. In addition, RNA-Seq experiments were performed. The comparison between Chip-Seq and RNA-Seq data has allowed us to identify 130 genes presenting both the binding of SETBP1 to their promoter region and transcriptional upregulation. Together these data suggest a role for SETBP1 as a transcriptional activator. Co-immunoprecipitation (Co-IP) experiments in transiently transfected HEK293T cells coupled with mass spectrometry (MS) analysis were performed to identify potential interactors of SETBP1. MS analysis led to the identification of the host cell factor 1 (HCF1), a component of the SET1/KMT2A COMPASS-like complex. Independent validation by western blot and fluorescence resonance energy transfer (FRET) confirmed the direct binding of HCF1 to SETBP1. Further independent experiments confirmed the Co-Ip of SET1/KMT2A and PHF8 with SETBP1. SET1/KMT2A is a core component of COMPASS-like complex and possesses H3K4 methyltransferase activity, whereas PHF8 possesses H4K20 demethylase activity. Both marks are associated with actively transcribed genes. Taken together, we have shown that SETBP1 protein is able to act as a transcriptional activator recruiting the HCF1/KMT2A/PHF8 complex.
In a previous study, comparing cytogenetic analysis and RNA-Seq to detect chromosomal abnormalities on AML patient samples, a new fusion between the ETS2 and ERG genes was reported. The patient carrying this fusion was affected by acute promyelocytic leukemia (APL) and did not respond to therapy with retinoic acid. The role of the ETS2-ERG fusion is not known. To gain insight about the functional role of ETS2-ERG fusion in APL two cellular models were established. HL-60 and NB-4 cells were stable transfected with retroviral empty vector or with a vector carrying the fusion gene. This vector also carries the GFP as a positive selection marker. HL-60 cells carrying the ETS2-ERG fusion treated with retinoic acid showed a decrease in the expression at membrane level of the differentiation marker CD11b. This suggests that the ETS2-ERG fusion is able to impair the differentiation of APL cells upon retinoic acid treatment. Further experiments are ongoing to confirm the data in the NB4 cellular model.
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VALLETTA, SIMONA. « Recurrent SETBP1 mutations in atypical chronic myeloid leukemia ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2014. http://hdl.handle.net/10281/50227.
Texte intégralRésumé :
Atypical chronic myeloid leukemia (aCML) is a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes. aCML shares clinical and laboratory features with Chronic Myeloid Leukemia (CML), but it lacks the Philadelphia chromosome and the resulting BCR-ABL fusion gene. This crucial difference with CML points to a different pathogenetic process. Because no specific recurrent genomic or karyotypic abnormalities have been identified in aCML, and the molecular pathogenesis of this disease has remained elusive with a dismal outcome, we performed exome-sequencing of eight aCML patients, in order to identify new possible recurrent mutations. The presence of an identical mutation not previously involved in cancer in two different aCML cases altering SETBP1 gene, prompted us to resequence this particular gene in samples from additional subjects with aCML or other hematological malignancies and in cell lines representative of the most common human solid cancers. SETBP1 mutations were identified only in aCML and in the closely related disorders and represents the first gene shown to be enriched and recurrently mutated in aCML. Most SETBP1 mutations were located between codons 858 and 871 causing abrogation of a degron binding site for E3-ubiquitin β-TrCP1 and protection from proteasomal degradation. This causes accumulation of SETBP1 and SET protein, decreased PP2A phosphatase activity and higher proliferation rates. Individuals with SETBP1 mutations had higher white blood cell counts and worse prognosis, indicating SETBP1 as a possible valuable diagnostic tool in the differential diagnosis of MDS/MPN syndromes and their prognosis.
This study increases the knowledge of the mechanisms by which malignancy arises and will have important consequences for the diagnosis, prognosis and treatment of aCML and diseases associated with SETBP1 alterations.
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Souza, Clarice de Azevedo. « The Acyl-CoA ligase-like (ACLL) gene family in Arabidopsis and poplar ». Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31283.
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Many genes of unknown function have been annotated in plant genome projects, and many of these may encode undiscovered enzymes. For example, completion of the Arabidopsis thaliana genome sequence revealed large families of phenylpropanoid-like enzymes of unknown functions. Using an in silico similarity search based on the amino-acid sequences of known Arabidopsis genes encoding 4-coumarate:CoA ligase (4CL), I identified nine putative genes as members of the Arabidopsis acyl-CoA ligase-like (ACLL) gene superfamily which encode a plant-specific clade of enzymes closely related to true 4CLs. I also identified all ACLLs in the fully sequenced poplar and rice genomes. Phylogenetic analysis of amino-acid sequences revealed five ACLL clades, each containing at least one ACLL member from each species, suggesting conserved biochemical functions for ACLL enzymes. In four of five clades, most of the ACLL representatives have the PTS1 peroxisomal target sequence, indicating a likely function in that organelle. I established tissue expression profiles and the wound and herbivory responsiveness of Arabidopsis and poplar ACLL genes, and this revealed similar expression patterns for potentially orthologous genes. Finally, I mined publicly available microarray databases for co-expressed Arabidopsis genes, and this data provides clues for potential ACLL biochemical functions. The only non-peroxisomal clade is the one most closely related to true 4CLs and contains a single copy gene in Arabidopsis (ACLL5) and poplar (ACLL13). These genes are flower and anther-preferred in expression, and because of the apparent conservation in sequence and in expression, were chosen for functional analysis. ACLL5 is transiently expressed in tapetum cells just prior to release of microspores from tetrads, suggesting a role in pollen wall and/or sporopollenenin formation. In support of this, an acll5 transposon insertion mutant is male sterile and fails to produce pollen grains. These data suggest that ACLL5 and similar enzymes from other species, produce CoA ester intermediates used in an unknown pathway required for pollen wall formation. In silico co-expression analysis in Arabidopsis has revealed potential other members of this pathway, also conserved across angiosperms. This work highlights the utility of the Arabidopsis model system in the discovery of genes in other plant species with genome sequence information.Science, Faculty of
Botany, Department of
Graduate
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Pomini, Armando Mateus. « Acil-homosserina lactonas produzidas pelas bacterias fitopatogenicas Pantoea ananatis e Methylobacterium mesophilicum e defesa quimica no opilião Hoplobunus mexicanus ». [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/249296.
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Orientador: Anita Jocelyne MarsaioliTese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica
Made available in DSpace on 2018-08-13T13:06:45Z (GMT). No. of bitstreams: 1 Pomini_ArmandoMateus_D.pdf: 4501241 bytes, checksum: 249f7514962993874b22ddcad9831cc8 (MD5) Previous issue date: 2009
As bactérias Gram-positivas e Gram-negativas possuem um mecanismo de comunicação química intra-específico conhecido como ¿quorum-sensing¿, regulando a expressão de uma vasta gama de atividades biológicas. As bactérias Gram-negativas utilizam acil-homosserina lactonas (acil-HSLs) como principais substâncias sinalizadoras. Na presente tese, relatamos a determinação da configuração absoluta do raro metabólito (S)-(-)-N-heptanoil-HSL produzida pela bactéria fitopatogênica Pantoea ananatis. A configuração absoluta desta substância foi determinada através da técnica de cromatografia gasosa com detecção por ionização em chama com coluna quiral, através de comparações de tempo de retenção e co-injeção com padrões sintetizados. Avaliou-se também a importância da configuração absoluta para a atividade antimicrobiana de acil-HSLs contra bactérias Gram-positivas (Bacillus subtilis, Bacillus cereus e Staphylococcus aureus). Curiosamente, o enantiômero não natural (R)-N-3-oxo-octanoil-HSL foi tão ativo quanto o produto natural (S). Estudou-se também as interações da (S)-N-3-oxo-octanoil-HSL com células de Agrobacterium tumefaciens NTL4(pZLR4) através da técnica de ressonância magnética nuclear de hidrogênio por diferença de transferência de saturação (STD-RMN), revelando que o primeiro evento de interação da substância com a célula ocorre com a região lipídica da membrana celular externa. Finalmente, realizou-se o estudo químico das substâncias sinalizadoras produzidas pela bactéria Methylobacterium mesophilicum, que ocorre simbioticamente com a bactéria Xylella fastidiosa nos vasos condutores de laranjeiras atacadas pela clorose variegada dos citros. Entre os vários resultados inéditos, reportamos a caracterização e síntese do produto natural inédito (S)-N-(2E)-dodecenoil-HSL e a primeira síntese do metabólito (S)-N-(2E, 7Z)-tetradecadienil-HSL. Outrossim, reportamos a primeira caracterização da configuração absoluta de cinco acil-HSLs naturais de cadeia longa. Realizou-se também estudos relacionados aos efeitos das acil-HSLs sintéticas contra bactérias Gram-positivas endofíticas da laranjeira. Adicionalmente, caracterizou-se a secreção de defesa do opilião Hoplobunus mexicanus. O repertório de defesa deste animal é composto por dois componentes voláteis de alta irritabilidade (2,5-dimetil-fenol e 2-metil-5-etil-fenol), além da tanatose e emissão de sons, uma característica inédita em opiliões
Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. In general, Gram-negative bacteria use acylated homoserine lactones (acyl-HSLs) as autoinducers, and Gram-positive bacteria use processed oligo-peptides. In the present work, we relate the absolute configuration determination of the rare metabolite (S)-(-)-N-heptanoyl-HSL produced by the phytopathogen Pantoea ananatis. The absolute configuration was determined by gas chromatography coupled to flame ionization detection with chiral column, through retention time comparison and co-injections with synthetic products. The importance of the absolute configuration for the antimicrobial activity of acyl-HSL against Gram-positive bacteria (Bacillus subtilis, Bacillus cereus and Staphylococcus aureus) was assessed. Curiously, non-natural (R)-N-3-oxo-octanoyl-HSL was as active as the natural product with (S) absolute configuration. The interaction of (S)-N-3-oxo-octanoil-HSL with Agrobacterium tumefaciens NTL4(pZLR4) cells was further studied using hydrogen nuclear magnetic resonance experiments with saturation transfer difference (STD-NMR) revealing that the first binding event is the diffusion through the lipidic part of the outer membrane. Finally, we have investigated the chemical study of the signaling substances produced by Methylobacterium mesophilicum, which co-occurs with Xylella fastidiosa in orange trees affected by the citrus variegated chlorosis disease. Among several results, we report herein the characterization and synthesis of a new natural product [(S)-N-(2E)-dodecenoyl-HSL], the first synthetic procedure for the rare (S)-N-(2E,7Z)-tetradecadienyl-HSL and the occurrence of a rare long, odd chain representative (N-tridecanoyl-HSL) in trace amounts. We report the first absolute configuration determination for five natural acyl-HSLs. We have also studied the effects of synthetic acyl-HSLs on Gram positive bacteria isolated from orange tissues. Additionally, the defensive secretion produced by the harvestman Hoplobunus mexicanus was characterized. The defensive repertory of this arachnid includes two irritating and volatile components (2,5-dimethyl-phenol and 2-methyl-5-ethyl-phenol), besides thanatosis and sound emission, a new behavioral artifice in opilionids
Doutorado
Quimica Organica
Doutor em Ciências
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Costa, Bruna Vieira de Lima. « Consumo de carnes e derivados e fatores associados ao estado nutricional de idosos em instiruição de longa permanência de Belo Horizonte - MG ». Universidade Federal de Minas Gerais, 2009. http://hdl.handle.net/1843/ACSL-7YAQLW.
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Sectional study, to identify the consumption of meat and meat products of elderly residents in geriatric institution of Belo Horizonte. Random sample (n = 52). Nutritional assessment was made by anthropometry, dietary and MAN. The process of acquisition, receipt, storage, handling of meat and meat products was observed. Was also carried out a cohort study to determine the anthropometric development. The results showed the need to reassess the process of buying, receiving and preparation of foodstuffs since there was a delivery of meat inappropriate amount and form of receipt, which contributed to a correction factor and per capita inadequate. The sample studied, 82.7% were women. The prevalence of overweight (BMI) was 46.1% and 23.1% underweight. According to MAN the prevalence of risk for malnutrition was 67.3%. According to the dietary analysis, the consumption of fat, polyunsaturated fatty acid and potassium had been insufficient in 100% of the elderly. The intake of B12 and zinc was inadequate in 44.2% and 82.7%, respectively, suggesting a low consumption of meat products. There was a prevalence of overweight and older people at high risk of diseases associated with obesity. However, from the MAN, there was a high rate of elderly people at risk for malnutritionEstudo seccional, objetivo de identificar o consumo de carnes e derivados de idosos residentes em Instituição Geriátrica de Belo Horizonte. Amostra aleatória simples (n=52). A avaliação nutricional foi composta pela antropometria, MAN e dietética. O processo de aquisição, recepção, armazenamento, manipulação da carne e derivados foi observado. Realizou-se também estudo de coorte para verificar a evolução antropométrica. Os resultados mostraram a necessidade de reavaliar o processo de compra, recebimento e preparo dos gêneros alimentícios já que se observou uma entrega inapropriada das carnes em quantidade e forma de recebimento, o que contribuía para um fator de correção e per capita inadequados. Da amostra estudada, 82,7% eram mulheres. A prevalência de sobrepeso (IMC) foi de 46,1% e de baixo peso 23,1%. Segundo a MAN a prevalência de risco para desnutrição foi 67,3%. Segundo a análise dietética, o consumo de lipídeo, ácido graxo poliinsaturado e potássio apresentaram-se insuficiente em 100% dos idosos. A ingestão de B12 e zinco foi insuficiente em 44,2% e 82,7%, respectivamente, o que sugere um baixo consumo de produtos cárneos. Observou-se uma prevalência de idosos com sobrepeso e com risco elevado de doenças associadas à obesidade. Em contrapartida, a partir da MAN, observou-se um alto índice de idosos com risco para desnutrição
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Teodoro, Bruno Gonzaga. « Função da Acil-CoA Sintetase 6 no metabolismo de músculo esquelético de ratos e humanos ». Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-29082016-100827/.
Texte intégralRésumé :
Cinco membros da família das Acil-CoA sintetases de cadeia longa (ACSL) são responsáveis por ativar ácidos graxos, produzindo acil-CoA, e distribuí-los entre diversas vias metabólicas no interior da célula, tais como a síntese de triacilglicerol (TAG) e ?- oxidação mitocondrial. Apesar das disfunções nas ACSLs contribuirem para muitas doenças metabólicasa função de algumas isoformas de ACSL em tecidos específicos permanece ainda sem descrição na literatura. Aqui mostramos pela primeira vez a presença de mRNA da ACSL6 no músculo esquelético de seres humanos. Além disso, indivíduos obesos apresentaram menores níveis de mRNA de ACSL6 quando comparados à indivíduos magros. Após refeição hiperlipídica aguda (high fat meal, HFM, 90% de gordura) a expressão ACSL6 aumentou 2,5 vezes em relação aos níveis de jejum. Nós também verificamos as condições metabólicas que controlam a expressão ACSL6 em ratos: o jejum de 48h modulou negativamente a expressão gênica de ACSL6 e de outros genes de síntese de lipídeos tais como SREBP-1c e DGAT1, enquanto que a ingestão aguda de HFM (80% de gordura saturada , 10 mL/kg) teve o efeito oposto; Após o treinamento aeróbio (6 semanas, 5 dias /semana, uma vez por dia, 60 min a 70% da capacidade aeróbica máxima) o mRNA da ACSL6 foi reduzido em 35%. Em células primárias de músculo esquelético de ratos, a transfecção com siRNA de ACSL6 diminuiu a expressão de ACSL6, DGAT1 e SREBP-1c e o acúmulo de TAGs e gotas lipídicas. O silenciamento gênico da ACSL6 também aumentou o conteúdo dos ácidos graxos C16:0 e C18:0, AMPK-fosforilada, capacidade respiratória mitocondrial, a oxidação de palmitato e mRNA de PGC-1?, UCP2 e UCP3, mas diminuiu a produção de espécies 11 reativas de oxigênio. Em células primárias de músculo esquelético de seres humanos, a superexpressão da ACSL6 não alterou o conteúdo de TAG e da proteína DGAT1, mas aumentou as espécies lipídicas esfingomielina e fosfatidilcolinas, e reduziu a oxidação de 1-14C-palmitato e a expressão do PGC1?. Em conclusão, ACSL6 está envolvida na síntese e distribuição de acil-CoA para a síntese de lipídeos. A inibição gênica da ACSL6 melhora a capacidade de respiração mitocondrial e oxidação lipídica, através da ativação da via AMPK/PGC1?.Five members of long-chain acyl-CoA synthetase (ACSL) family activate fatty acids providing acyl-CoA for several metabolic pathways within the cell, such as synthesis of triacylglycerol (TAG) and mitochondrial ?-oxidation, and their dysfunctions contribute to many metabolic diseases. Despite this, the existence and function of some ACSL isoforms in specific tissues remains unclear. Here we show for the first time the presence of ACSL6 mRNA and protein in skeletal muscle (SM) of humans. Obese subjects had lower levels of ACSL6 mRNA when compared to leans, and acute high fat meal (HFM, 90% fat) increased ACSL6 expression 2.5 times over fasted levels in both. We also verify the metabolic conditions that control ACSL6 expression in rats: fasting (48h) negatively modulated the ACSL6 mRNA and the expression of other genes of lipid synthesis SREBP-1c and DGAT1 in rat SM, while acute ingestion of HFM (80% saturated fat, 10 mL/Kg) had the opposite effect; After aerobic training (6 weeks, 5 days/week, once a day, 60 min at 70% of maximal aerobic capacity) ACSL6 mRNA was reduced 35%. In primary skeletal muscle cells (PSMC) of rats, ACSL6-specific siRNA oligo transfection (20 nM) decreased ACSL6, DGAT1 and SREBP-1c mRNA and the accumulation of TAGs and lipid droplets (LD). The knockdown also increased the content of C16:0 and C18:0 fatty acids, AMPK-Phosphorylated, mitochondrial content and respiratory rates, palmitate oxidation and PGC-1?, UCP2 and UCP3 mRNA, but decreased reactive oxygen species production. In PSMC of humans, ACSL6 overexpression did not change the contents of TAG or DGAT1 mRNA, but increased sphingomyelin and phosphatidylcholines and reduced 14C-palmitate oxidation and PGC1? mRNA expression. In conclusion, ACSL6 drives acyl-CoA toward lipid synthesis and its 13 downregulation improves mitochondrial capacity of respiration, lipid oxidation and biogenesis, which involves the activation of AMPK/PGC1-? pathway.
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Al-Faiyz, Yasair S. S. « The chemistry of O-acyl derivatives of N-acyl hydroxamic acid ». Thesis, University of Warwick, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252534.
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Chalfoun, David Joseph. « Acyl transfer to lysine : an investigation acyl transfer across large rings ». Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/38769.
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Chrystiuk, E. « Acyl group transfer mechanisms ». Thesis, University of Kent, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374300.
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Miranda, Anabela Medo. « Mycobacterial acyl-CoA carboxylases ». Thesis, University of Surrey, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298085.
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Cardoso, Ariel Rodrigues. « Geração de espécies reativas de oxigênio (ERO) mitocondriais : papel das Acil-CoA desidrogenases de cadeia muito longa ». Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-23012015-134052/.
Texte intégralRésumé :
Dietas hiperlipídicas e a esteatose hepática são condições extremamente prevalentes. Trabalhos anteriores mostraram que a esteatose está associada a um aumento na geração de espécies reativas de oxigênio (ERO), e que isso pode mediar danos no fígado. Neste trabalho nós investigamos os possíveis mecanismos que desencadeiam os aumentos nas taxas de geração de ERO por meio da administração de dietas hiperlipídicas. Nós descobrimos que mitocôndrias de animais sujeitos a dietas hiperlipídicas não apresentaram diferenças significativas quanto a capacidade respiratória máxima e acoplamento, mas eram capazes de gerar mais ERO especificamente quando usados substratos do metabolismo de ácidos graxos. Além disso, foi observado que muitas isoformas de acil-CoA desidrogenases estavam mais expressas nos fígados de animais alimentados pela dieta hiperlipídica. No entanto, quando realizados ensaios de atividade enzimática apenas a acil CoA desidrogenase de cadeia longa (VLCAD) foi mais ativa. Estudos conduzidos com mitocôndrias permeabilizadas e expostas a grupos acil-CoA de diferentes tamanhos sugerem que a VLCAD pode ser uma fonte da produção aumentada de ERO em animais submetidos a dietas hiperlipídicas. Esta produção foi estimulada pela ausência de NAD+. Concluindo, nossos estudos descobriram uma nova fonte importante na geração de ERO estimulada por dietas hiperlipídicas, a VLCADHigh fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis occurs concomitantly with enhanced reactive oxygen species (ROS) generation, which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is a source of enhanced ROS production in mitochondria from HFD animals. This production is stimulated by the lack of NAD+. Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS
14
Bromley, L. A. « Iron acyl complexes in synthesis ». Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237924.
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Kenny, Jane Ruth. « An investigation of acyl glucuronides ». Thesis, University of Liverpool, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269597.
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Levy, Esther Gillian. « Porphyrin-catalysed acyl transfer reactions ». Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627031.
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Ioakem, Nicolle. « Acme Tool 2.0 Software Manual ». Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/245076.
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Idnani, Sunil Charan 1964. « An ACSL interface for DYMOLA ». Thesis, The University of Arizona, 1991. http://hdl.handle.net/10150/291863.
Texte intégralRésumé :
This MS thesis proposes the use of DYMOLA, an object-oriented language for modeling hierarchically structured systems, to generate ACSL simulation programs for continuous system analysis. An ACSL model described in terms of time dependent non-linear differential equations or transfer functions can be generated from a hierarchical model description of the system using DYMOLA. The model description in DYMOLA can be an equation description or a non-linear hierarchical bond graph abstraction to describe the system under investigation. The interface provides an automated method to generate ACSL simulation programs, hence eliminating the need for manual coding. The provision to specify an experiment description for run-time analysis and additional model statements is implemented. The implementation of the compiler's code generator includes parsing, error checking and system dependent file handling routines. Implementation techniques, model and control file specifications, and validation with examples in several application areas are described.
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Jesus, Jacqueline Cristina Bueno Janice de. « Síntese e caracterização espectroscópica de complexos tris -dicetonatos do íon európio com ligantes 2-(n-acil)-piridina ». Universidade Federal da Paraíba, 2014. http://tede.biblioteca.ufpb.br:8080/handle/tede/7153.
Texte intégralRésumé :
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In this work, we propose a new class of complexes of trivalent europium ion derived from tetrakis-diketonates, by replacing the keto group of a ligand by the 2- aminopyridyl. For the synthesis of these complexes, the amides N-acetyl-2- aminopyridine and N-trifluoroacetyl-2-aminopyridine were prepared via acylation of 2- aminopyridine and their respective anhydrides. N-benzoyl-2-aminopyridine was synthesized by basic hydrolysis of N, N-dibenzoyl-2-aminopyridine. The ligands were characterized by mass spectrometry, melting point measurement and absorption spectroscopy in the infrared region. New compounds have been obtained, having the formulas [Eu(BZAC)3(NAC2AP)] and [Eu(TTA)3(NTF2AP)2]. These complexes were characterized by complexometric titration, CHN elemental analysis and infrared absorption spectroscopy. Through the results obtained by photoluminescence spectroscopy, the analysis of the split of the transitions 5D0 → 7FJ in emission spectra, leads to the inference that the Eu3+ ion in the complex [Eu(TTA)3(NTF2AP)2] is in a chemical environment of higher symmetry as compared to its precursor complex. Both complexes [Eu(BZAC)3(NAC2AP)] and [Eu(TTA)3(NTF2AP)2] showed quantum efficiencies higher than the corresponding aqua complex and tetrakisdiketonates. This result indicates that replacing the fragment R(CO)CH- of a ligand in the tetrakis-diketonate complex by an 2-aminopyridyl group is a good strategy to generate highly luminescent complexes. This strategy can be used in the development of efficient light conversion molecular devices such as those desirable for biomarkers.
No presente trabalho, foi proposta uma nova classe de complexos de íon európio trivalente derivados dos tetrakis-dicetonatos, por substituição do grupo ceto de um dos ligantes pelo grupo 2-aminopiridil. Para síntese desses complexos foram preparadas as amidas N-acetil-2-aminopiridina e N-trifluoroacetil-2-aminopiridina via acilação da 2-aminopiridina com seus respectivos anidridos. A N-benzoil-2- aminopiridina foi sintetizada através da hidrólise básica da N,N-dibenzoil-2- aminopiridina. Os ligantes sintetizados foram caracterizados por espectrometria de massas, determinação de ponto de fusão e espectroscopia de absorção na região do infravermelho. Foram obtidos complexos inéditos, cujas fórmulas são [Eu(BZAC)3(NAC2AP)] e [Eu(TTA)3(NTF2AP)2], caracterizados por titulação complexométrica, análises elementar de carbono, hidrogênio e nitrogênio, além de espectroscopia de absorção na região do infravermelho. Por meio dos resultados obtidos por espectroscopia de fotoluminescência, analisando os desdobramentos das transições 5D0→7FJ, nos espectros de emissão, pode-se inferir que o íon Eu3+ no complexo [Eu(TTA)3(NTF2AP)2] encontra-se em um ambiente químico de maior simetria se comparado ao seu aqua-complexo precursor. Ambos os complexos [Eu(BZAC)3(NAC2AP)] e [Eu(TTA)3(NTF2AP)2] apresentaram eficiências quânticas superiores aos correspondentes tris-dicetonatos aquosos e tetrakis-dicetonatos. Este resultado indica que a substituição do fragmento R(CO)CH- pelo grupo 2-aminopiridil de um dos ligantes dos complexos tetrakis-dicetonatos de Eu3+ seja uma boa estratégia para gerar complexos altamente luminescentes. Tal estratégia poderá ser utilizada no desenvolvimento de Dispositivos Moleculares Conversores de Luz eficientes, tais como os desejáveis para biomarcadores.
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Conocimiento, Dirección de Gestión del. « ACM Digital Library ». Asociación de Maquinaria de Computación, 2004. http://hdl.handle.net/10757/655259.
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Reis, Barbaros. « Addition Of Acyl Phosphonates To Ethylcyanoformate ». Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12609090/index.pdf.
Texte intégralRésumé :
Functionalized cyanophosphates are important starting materials for the synthesis of
beta-lactam ring moiety of beta-lactam antibiotics. The cyanophosphates are
synthesized starting from easily available acylphosphonate and ethylcyanoformate.
Acylphosphonates are synthesized starting from acylchloride and trimethylphosphite.
Addition of acylphoshonate to ethylcyanoformate furnishes the cyanophosphate with
the quaternary center.
22
Walker, Jonathan Charles. « Asymmetric synthesis via iron acyl complexes ». Thesis, University of Oxford, 1986. http://ora.ox.ac.uk/objects/uuid:55cfc478-5868-474f-9d2b-532218ec6fd6.
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Aman, Ahmed M. « Studies of amide acyl transfer reactions ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0028/NQ38297.pdf.
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Wills, M. « Synthetic application of iron acyl complexes ». Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235128.
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Easton, R. J. C. « Stereoselective synthesis via iron acyl complexes ». Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379991.
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Ayscough, A. P. « Stereoselective synthesis using iron acyl complexes ». Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234993.
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Preston, Simon Christopher. « Asymmetric synthesis via iron acyl complexes ». Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236153.
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Fraser-Bell, G. « Asymmetric synthesis via iron acyl compounds ». Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329923.
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29
Penman, June. « GPR55 and N-acyl amino acids ». Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/2e07c280-3a61-4f49-a9da-1fa4ffc79fa5.
Texte intégralRésumé :
G-protein coupled receptor 55 (GPR55) is a novel lipid sensing receptor activated by the endogenous lipid, lysophosphatidylinositol (LPI) and is reported as a putative cannabinoid receptor. However GPR55 shares limited homology with the two cloned cannabinoid receptors (CB1 and CB2) but does exhibit some cannabinoid sensitivity. Recently a family of bioactive lipids, the N-acyl amino acids, are gaining interest due to their structural similarity to endocannabinoids (naturally occurring CB1 and CB2 agonists). N-acyl amino acids have little or no affinity for either CB1 or CB2 and many have no known biological target at present. This study used a subset of N-acyl amino acids; possessing either a serine or glycine head group attached to varying fatty acid chains; to assess these novel lipids as potential GPR55 ligands. Three cell lines were utilised, a stably transfected HEK293 cell line that overexpresses 3xHA N-terminus tagged hGPR55 (hGPR55-HEK293 cells) and control HEK293 cells. In addition, the DU145 a prostate cancer cell line which is reported to endogenously express GPR55 was investigated. N-acyl amino acid challenge activated GPR55 to promote Ca2+ mobilisation, CREB phosphorylation, actin cytoskeletal reorganisation and elongation of focal adhesions. Furthermore GPR55-mediated downstream signalling effectors were studied comparing LPI to the orphan lipid; N oleoyl-L-serine (NOSer). This study highlights that N-acyl amino acids act as GPR55 agonist/partial agonists in hGPR55-HEK293 cells. Both LPI and NOSer exert effects in prostate cancer cells (DU145s) which are GPR55 mediated. GPR55 may exhibit ligand bias as LPI was more efficacious in Ca2+ mobilisation. However in the pCREB assay NOSer was more efficacious than LPI. A similar efficacy and potency to either LPI or NOSer was observed in the other assays in both hGPR55-HEK293 and DU145 cells. Furthermore this study is the first where a named GPCR can be assigned for responses that are mediated by NOSer.
30
Wallace, Paul Neil. « Acyl transfer reactions of diphenylphosphine oxides ». Thesis, University of Cambridge, 1986. https://www.repository.cam.ac.uk/handle/1810/270447.
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Bailey, Mark J. « Acyl glucuronide reactivity : some biological consequences / ». [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16205.pdf.
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Othman, Abrizah. « Isolation and characterisation of an acyl-acyl carrier protein (ACP) thioesterase gene from the oil palm (Elaeis guineensis) ». Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404314.
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AIT, MANSOUR HAMID. « Recherches dans la serie des acyl-6 benzoxazolinones : metabolites de la benzoyl-6 benzoxazolinone et pharmacomodulation des derives halogenoacyles ». Lille 2, 1991. http://www.theses.fr/1991LIL2T007.
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AICHAOUI, HOCINE. « Acyl benzoxazolinones et produits de transformation : synthese, structure et proprietes pharmacologiques ». Lille 2, 1991. http://www.theses.fr/1991LIL2T001.
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Poderi, Cecilia. « Synergistic catalysis : Michael addition of acyl-pyridines ». Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/14409/.
Texte intégralRésumé :
A new diastereo- and enantioselective strategy for the functionalization of 2-acetyl-pyridine with α,β-unsaturated aldehydes has been investigated through synergistic catalysis. In particular, the aim of the work was to use cinnamaldehydes bearing different substituents on the phenyl group and to study its effect on the yield, conversion and stereoselectivity of the reaction. The reaction mechanism involves combined iminium ion and transition metal catalysis in a synergistic fashion and proceeds with two consecutives Michael additions, followed by final intramolecular aldol condensation to yield the formation of three new stereogenic carbons, with high to excellent stereoselectivities. The structures of the molecules obtained were fully characterized by NMR spectroscopy. After having assigned the relative configuration by NOE-NMR and 2D-COSY experiments, conformational analysis was performed by DFT calculations to find the most stable molecular conformations. The absolute configuration of each diastereoisomer was then eventually assigned by quantum mechanical simulations of the Electronic and Vibrational Circular Dichroism spectra.
36
Sevim, Ilhan. « Reactions Of Diethylaluminum Cyanide With Acyl Phosphonates ». Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12611557/index.pdf.
Texte intégralRésumé :
This thesis includes reaction of diethylaluminum cyanide with acyl phosphonates. Cyanohidrin O-phosphates are synthesized from easily available acyl phosphonates and diethylaluminum cyanide. Synthesis of cross-benzoin product of acyl phosphonate, α
-hydroxy phosphonate and tertiary carbinol are synthesized from the reaction of diethylaluminum cyanide with acyl phosphonates, representatively. Asymmetric syntheses of cyanohydrin and benzoin type reaction of acyl phoshonate are also investigated representatively.
37
Wang, Xueqing. « Oxidative cyclization of phenolic N-acyl sulfonamides ». Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/61303.
Texte intégralRésumé :
The oxidative activation of appropriately substituted phenols with a hypervalent iodine reagent, in the presence of suitable nitrogen nucleophiles, results in formation of 2- or 4-amidodienones. The process is described as the oxidative amidation of phenols. The dienones thus produced are useful building blocks for the synthesis of alkaloids. The nitrogen nucleophile may be an oxazoline, a sulfonamide or phosphoramide (intramolecular reactions), or a nitrile (bimolecular reaction), but not a carboxamide. This is because carboxamides express Onucleophilicity toward oxidatively activated phenols, resulting in formation of iminolactones, which are readily hydrolyzed to lactones upon workup.
This present thesis describes efforts to extend oxidative amidation chemistry to carboxamides. The behavior of phenolic N-acyl sulfonamides was thus explored. The product obtained upon oxidative cyclization of these substrates proved to be dependent upon their structure. In many cases, N-sulfonyl iminolactones were thus obtained. These heretofore undocumented products proved to be surprisingly stable and resistant to hydrolysis.Science, Faculty of
Chemistry, Department of
Graduate
38
Doran, John D. « Raman spectroscopic studies of acyl cysteine proteases ». Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/9624.
Texte intégralRésumé :
For a series of acyl cysteine proteases structure-reactivity relationships for the deacylation step have been established using a combination of Raman and absorption spectroscopies and enzyme kinetics. The simple chromophoric ligand 5-methylthienylacryloyl- (5MTA-) and three novel peptide based substrates labelled with the 5MTA- moiety, were used to create acyl enzyme adducts with papain, cathepsin B, cathepsin L, and protein engineered mutants of cathepsins B and L. The chromophoric specific substrates, 2-Ethoxycarbamido-3-(5-methylthienyl)acryloyl ethyl ester (NHCOOEt5MTAEt), 2-(N-acetyl-L-alanine)amino-3(5-methylthienyl)acryloyl ethyl ester (Ala5MTAEt), and 2-(N-acetyl-L-phenylalanine)amino-3-(5-methylthienyl) acryloyl ethyl ester (Phe5MTAEt), were designed to utilize hydrogen bonding and hydrophobic interactions which are known to promote catalysis in papain. For cathepsins B and L removing one of the hydrogen bonding groups making up the oxyanion hole reduces the deacylation rate 3-25 fold with the tour substrates. The deacylation rate constants for the acyl cysteine protease series span a 214 fold range, from 0.07 to 15 $\times$ 10$\sp{-3}$ sec$\sp{-1}$. Using $\sp $C=O substitution it is possible to detect the acyl C=O frequency, $\nu\sb{\rm C-O}$, for each acyl cysteine protease in the Raman difference spectrum. A correlation between the $\nu\sb{\rm C-O}$ frequency and the deacylation rate constant was established, where $\nu \sb{\rm C-O}$ increases with increasing reactivity. This trend is the opposite to that seen with acyl serine proteases. The opposite trend for acyl cysteine proteases is ascribed to the strong electron polarizing forces in the active site, due principally to an $\alpha$ helix dipole, which change the hybridization about the carbonyl carbon atom. A correlation was also established between the absorption maximum, $\lambda\sb{\rm max}$, and the deacylation rate constant. As the deacylation rate increases, 214 fold across the series, $\lambda\sb{\rm max}$ red shifts from 367 to 384 nm. It is proposed that differential interactions between the $\alpha$-helix dipole in the active site of the proteins and the $\pi$-electrons in the bound chromophoric substrate are responsible for these changes in $\lambda\sb{\rm max}$, with increasing red shifts being caused by more favourable $\alpha$-helix dipole-substrate interactions in the excited electronic state. It is also proposed that similar interactions occur between the $\alpha$-helix dipole and the transition state of the acyl enzyme on the reaction pathway, giving rise to the observed differences in deacylation rates. These results demonstrate the importance of $\alpha$-helix dipoles in cysteine protease active sites in modulating enzymatic activity, and provide the first experimental evidence for the role of $\alpha$-helix dipoles in catalysis.
39
Obuchowska, Agnes K. « Acyl transfer in chemical synthesis of oligosaccharides ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ34056.pdf.
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Hellenbrand, Janine [Verfasser]. « Charakterisierung von Acyl-CoA-Reduktasen / Janine Hellenbrand ». Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2012. http://d-nb.info/1022733494/34.
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Beattie, Stuart Gavin. « Lecithin colesterol ACYL transferase gene transfer studies ». Thesis, Royal Holloway, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409233.
Texte intégral
42
Warner, P. « Asymmetric synthesis via transition metal acyl complexes ». Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355823.
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Simonian, Houri. « Acyl radical mediated polyene cyclisations in synthesis ». Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307815.
Texte intégral
44
Luthra, A. K. « Some studies of acyl-group transfer reactions ». Thesis, University of Kent, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332147.
Texte intégral
45
Maddaford, Adrian. « Studies toward an enantioselective acyl transfer catalyst ». Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324425.
Texte intégral
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Klair, Sukhbinder S. « Stereoselective enolate alkylation of acyl dithiane oxides ». Thesis, University of Liverpool, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314512.
Texte intégral
47
Fraser, Thomas Colin Michael. « Characterisation of sunflower lysophosphpatidylcholine Acyl-CoA acyltransferase ». Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238923.
Texte intégral
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Atkinson, Benjamin. « Metal catalysed acyl transfer reactions of amides ». Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665412.
Texte intégralRésumé :
The following thesis outlines work carried out during the last three years for the development and investigation of methodologies using amides as N- and O- acylating agents. Chapter 1 highlights the range of methodologies and protocols reported in the literature that use amides as precursors for the synthesis of both functionalised amides and esters. The introduction will highlight the range of catalysts and promoters used as well as the scope of the current methodologies. As well as this it will highlight the limitations of the methodologies so emphasising where the following research fits into these areas. Chapter 2 presents the development of a transamidation methodology using zirconocene dichloride as a catalyst. The scope with respect to functional group tolerance is presented as well as the investigations into the mechanism of the reaction. Chapter 3 builds on the research presented in Chapter 2 and details the development of a more catalytically active zirconocene transamidation methodology. By the addition of a catalytic additive the temperature or time required for the reaction to be carried out could be lowered. Investigations into the mechanism were also carried out highlighting the in situ formation of an active catalytic species. Chapter 4 details the development of an operationally simple methodology for the O-acylation of alcohols using amides. Using a catalytic amount scandium triflate the substrate scope of the reaction was explored with a proposed mechanism presented based on activation of the amide.
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Chhatwal, Amarjit. « Novel approaches to catalytic acyl transfer reactions ». Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665422.
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50
Tyler, Lydia Justine. « Chemical reactions of an acyl carrier protein ». Thesis, University of Cambridge, 1996. https://www.repository.cam.ac.uk/handle/1810/272174.
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