Página 1 dos resultados de 5613 itens digitais encontrados em 0.004 segundos

‣ Adsorption of phenylalanine onto polymeric resins: equilibrium, kinetics and operation of a parametric pumping unit

Díez, Sergi; Leitão, Anabela; Ferreira, Licínio; Rodrigues, Alírio
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
Relevância na Pesquisa
36.634153%
Adsorption of -Phenylalanine onto polymeric adsorbents (Amberlite XAD-4 and XAD-16; Sephabeads SP206 and SP207) was studied. Adsorption equilibrium isotherms were measured by batch equilibration at 15 and 40°C, showing the possibility of using a parametric pumping technique for aminoacid purification/recovery. Dynamic studies in a laboratory adsorption column Amicon Column (22 × 500 mm) were carried out to further screen adsorbents and obtain mass transfer parameters to be used in the modeling, simulation and operation of the pilot parametric pumping unit. The pilot plant includes a Amicon Columnn (90 × 1000 mm) and is completely automated. A package for the simulation of this cyclic operation was developed. Simulated and experimental results using Sephabeads SP206 (Mitsubishi Kasei Corporation, Japan) are in good agreement.; http://www.sciencedirect.com/science/article/B6THJ-3V7PF1M-3/1/790b48ad004d05db3bbf0582f73002e8

‣ The active site residue tyrosine 325 influences iron binding and coupling efficiency in human phenylalanine hydroxylase

Miranda, Frederico F.; Kolberg, Matthias; Andersson, K. Kristoffer; Geraldes, Carlos F. G. C.; Martínez, Aurora
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
Relevância na Pesquisa
36.634153%
Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH4)-dependent enzyme that catalyzes the hydroxylation of l-Phe to l-Tyr. The non-heme iron in the enzyme (Fe(III) as isolated) is 6-coordinated to a 2-His-1-carboxylate motif and three water molecules (wat1, wat2 and wat3). Tyr325 is at the second coordination sphere, hydrogen-bonded to water (wat1). We prepared and expressed mutants with Leu, Ala, Ser and Phe at this position. Only Y325L and the conservative mutation Y325F resulted in stable enzymes, but the mutant Y325F has been found to be post-translationally hydroxylated and to revert back to wild-type PAH [S.D. Kinzie, M. Thevis, K. Ngo, J. Whitelegge, J.A. Loo, M.M. Abu-Omar, J. Am. Chem. Soc. 125 (2003) 4710-4711], being inadequate to investigate the early inferred functional role of Tyr325. On the other hand, compared to wild-type PAH, Y325L shows reduced specific activity, decreased coupling efficiency and decreased iron content. The mutant also reveals a very high affinity for l-Phe and BH4 and does not manifest positive cooperativity for the substrate. All together, our results support that the mutation Y325L causes the removal or increased delocalization of the iron-ligated wat1 and, in turn, a less tight binding of the metal. Tyr325 thus appears to have an important role ensuring stoichiometric binding of iron...

‣ Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency; Responsividade à tetrahidrobiopterina em pacientes com deficiência de fenilalanina hidroxilase

Giugliani, Luciana; Sitta, Angela; Vargas, Carmen Regla; Silva, Luiz Carlos Santana da; Nalin, Tatiéle; Pereira, Maria Luiza Saraiva; Giugliani, Roberto; Schwartz, Ida Vanessa Doederlein
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
Relevância na Pesquisa
36.759856%
Objetivo: Identificar indivíduos responsivos à tetrahibrobiopterina (BH4) em uma amostra de pacientes brasileiros com hiperfenilalaninemia por deficiência de fenilalanina-hidroxilase (HPA-PAH). Métodos: Estudo intervencional, amostragem por conveniência. Para serem incluídos no estudo, os pacientes deveriam: possuir diagnóstico bioquímico de HPA-PAH; ter idade ≥ 7 anos; estar em tratamento dietético; e apresentar níveis de fenilalanina (Phe) ≥ 6 mg/dL em todas as medidas realizadas no ano anterior à inclusão no estudo. Os níveis de Phe foram determinados por meio de espectrometria de massas in tandem no dia anterior (dia 1) e nos pontos de hora 0, 4 e 8 h (dia 2) e 24 h (dia 3) após ingestão de BH4. Os critérios utilizados para definir responsividade ao BH4 foram: critério 1-redução ≥ 30% de Phe após 8 h da administração de BH4; e critério 2-redução ≥ 30% de Phe após 24 h da administração. Resultados: Dezoito pacientes foram incluídos no estudo (mediana de idade = 14 anos, sexo masculino = 12). Cinco pacientes foram responsivos ao BH4, sendo três (forma clássica: um; forma leve: dois) de acordo com ambos os critérios, e dois (forma clássica: um; forma não definida: um) de acordo com o critério 2. Os níveis de Phe plasmáticos do dia 1 não demonstraram variação nos pontos de hora (p = 0...

‣ Peroxidase and phenylalanine ammonia-lyase activities, phenolic acid contents, and allelochemicals-inhibited root growth of soybean

Herrig, V; De Lourdes, M.; Ferrarese, MDL; Suzuki, L. S.; Rodrigues, J. D.; Ferrarese, O.
Fonte: Sociedad Biolgia Chile Publicador: Sociedad Biolgia Chile
Tipo: Artigo de Revista Científica Formato: 59-66
Português
Relevância na Pesquisa
36.634153%
The influence of the allelochemicals ferulic (FA) and vanillic (VA) acids on peroxidase (POD, EC 1.11.1.7) and phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) activities and their relationships with phenolic acid (PhAs) contents and root growth of soybean (Glycine max (L.) Merr.) were examined. Three-day-old seedlings were cultivated in nutrient solution containing FA or VA (0.1 to 1 mM) for 48 h. Both compounds (at 0.5 and 1 mM) decreased root length (RL), fresh weight (FW) and dry weight (DW) and increased PhAs contents. At 0.5 and 1 mM, FA increased soluble POD activity (18% and 47%, respectively) and cell wall (CW)-bound POD activity (61% and 34%), while VA increased soluble POD activity (33% and 17%) but did not affect CW-bound POD activity. At I mM, FA increased (82%) while VA reduced (32%) PAL activities. The results are discussed on the basis of the role of these compounds on phenylpropanoid metabolism and root growth and suggest that the effects caused on POD and PAL activities are some of the many mechanisms by which allelochemicals influence plant growth.

‣ Chemopreventive activity of phenylalanine against damage mutagenic prompted by the acute administration of cyclophosphamide in pregnant and non-pregnant mice using the micronucleus test

Mauro,Mariana de Oliveira; Pesarini,João Renato; Ishii,Priscila Lumi; Silva,Ariane Fernanda da; Oliveira,Rodrigo Juliano
Fonte: Sociedade Brasileira de Farmacognosia Publicador: Sociedade Brasileira de Farmacognosia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2010 Português
Relevância na Pesquisa
36.84501%
This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24% and 31.64% for G5 and G6, respectively, at T24, and 29.32% and 24.13% for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25% in G5 and G6 at 18.47%. At T48 the harm-reduction percentages were 44.67% and 37.76% for G5 and G6, respectively.

‣ Complexes of thallium(I) and cadmium(II) with dipeptides of L-phenylalanylglycine and Glycyl-L-phenylalanine

Sharifi,Sasan; Nori-shargh,Davood; Bahadory,Azar
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2007 Português
Relevância na Pesquisa
36.84501%
The stability constants of the complexes of thallium(I) and cadmium(II) ions with dipeptides of glycyl-L-phenylalanine and L-phenylalanylglycine were determined in aqueous solution at 25 ºC and 0.1 mol dm-3 ionic medium using a combination of potentiometric and spectrophotometric techniques. Sodium perchlorate was used to maintain the ionic strength. The composition of the formed complexes was determined and it was shown that thallium(I) and cadmium(II) forms two mononuclear 1:1 species with the ligands, of the type [Tl(HL)]+, TlL, [Cd(HL)]2+ and [CdL]+ in the pH range of study (1.5-10.5), where L represents a fully dissociated ligand. The logarithms of the cumulative stability constants, betaxyz, of the complexes, [(Metal ion)x(H+)y(ligand) z], are log beta111 and log beta101: 12.15, 3.39 (for Tl+ with L-phenylalanylglycine), 11.36, 2.13 (for Tl+ with glycyl-L-phenylalanine), 12.06, 2.82 (for Cd2+ with L-phenylalanylglycine), 10.70 and 1.70 (for Cd2+ with glycyl-L-phenylalanine), respectively.

‣ Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China

Zhou,Yong-An; Ma,Yun-Xia; Zhang,Quan-Bin; Gao,Wei-Hua; Liu,Jian-Ping; Yang,Jian-Ping; Zhang,Gai-Xiu; Zhang,Xiao-Gang; Yu,Liang
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 Português
Relevância na Pesquisa
36.634153%
The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%), followed by Ivs7 +2T>A (5.1%) and T278I (2.5%). G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.

‣ cDNA cloning, Phylogenic Analysis and Gene Expression Pattern of Phenylalanine ammonia-lyase in Sugarcane (Saccharum officinarum L.)

Hashemitabar,Mahmoud; Kolahi,Maryam; Tabandeh,Mohammad Reza; Jonoubi,Parisa; Majd,Ahmad
Fonte: Instituto de Tecnologia do Paraná - Tecpar Publicador: Instituto de Tecnologia do Paraná - Tecpar
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2014 Português
Relevância na Pesquisa
36.634153%
The aim of the present study was to clone and characterize a full length cDNA of sugarcane (Saccharum officinarum) phenylalanine ammonia-lyase (SoPAL). Differential tissue expression pattern of the SoPAL transcript and its enzyme activity was also analyzed during the tillering stage of growth. The full-length of SoPAL cDNA was 2118 bp long and contained a protein with 706 amino acids, determined by encoding technique. The amino acid sequence and phylogenic analysis of the cloned SoPAL showed high similarity to PAL from other monocotyledonous such as sorghum (96%), maize (93%) and Bamboos (87.12%). The highest levels of SoPAL transcript were observed in the root and stem, while its minimal gene expression levels were in the leaves and sheath, respectively. The highest level of SoPAL enzyme activity was in the leaves. These results helped to understanding the characteristics of PAL biosynthesis and its regulation at the molecular level in sugarcane. This information could be critical for the manipulation of phenylpropanoid biosynthesis in the plant using biotechnological processes.

‣ Mis-Regulation of 3-Deoxy-d-Arabino-Heptulosonate 7-Phosphate Synthetase Does Not Account for Growth Inhibition by Phenylalanine in Agmenellum quadruplicatum

Jensen, Roy A.; Stenmark-Cox, S.; Ingram, Lonnie O.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1974 Português
Relevância na Pesquisa
27.107197%
The growth of the blue-green bacterium, Agmenellum quadruplicatum, is inhibited in the presence of l-phenylalanine. This species has a single, constitutively synthesized 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthetase. l-Phenylalanine inhibits DAHP synthetase non-competitively with respect to both substrate reactants. Other aromatic amino acids do not inhibit the activity of DAHP synthetase. A common expectation for branch-point enzymes such as DAHP synthetase is a balanced pattern of feedback control by all of the ultimate end products. It seemed likely that growth inhibition might equate with defective regulation within the branched aromatic pathway. Accordingly, the possibility was examined that mis-regulation of DAHP synthetase by l-phenylalanine in wild-type cells causes starvation for precursors of the other aromatic end products. However, the molecular basis for growth inhibition cannot be attributed to l-phenylalanine inhibition of DAHP synthetase for the following reasons: (i) DAHP synthetase enzymes from l-phenylalanine-resistant mutants are more, rather than less, sensitive to feedback inhibition by l-phenylalanine. (ii) Shikimate not only fails to antagonize inhibition, but is itself inhibitory. (iii) Neither the sensitivity nor the completeness of l-phenylalanine inhibition of the wild-type enzyme in vitro appears sufficient to account for the potent inhibition of growth in vivo by l-phenylalanine. The dominating effect of l-phenylalanine in the control of DAHP synthetase appears to reflect a mechanism that prevents rather than causes growth inhibition by l-phenylalanine. The alteration of the control of DAHP synthetase in mutants selected for resistance to growth inhibition by l-phenylalanine did indicate that the cause for this metabolite vulnerability can be localized within the aromatic amino acid pathway. Apparently...

‣ Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man.

Krause, W; Halminski, M; McDonald, L; Dembure, P; Salvo, R; Freides, D; Elsas, L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1985 Português
Relevância na Pesquisa
27.094478%
Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients plasma phenylalanine rose (900-4,000 microM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient...

‣ The contribution of phenylalanine to tyrosine metabolism in vivo. Studies in the post-absorptive and phenylalanine-loaded rat.

Moldawer, L L; Kawamura, I; Bistrian, B R; Blackburn, G L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/03/1983 Português
Relevância na Pesquisa
27.144824%
1. Rates of appearance and oxidation of plasma L-leucine, L-phenylalanine and L-tyrosine, as well as conversion of plasma phenylalanine into plasma tyrosine, were determined in 90-120 g rats after overnight starvation and while receiving 115-120 mumol of L-phenylalanine/h. 2. In the post-absorptive state, plasma tyrosine and phenylalanine appearances were similar, despite the fact that 22% of plasma tyrosine appearance could be attributed to the hydroxylation of phenylalanine. 3. A constant infusion of 115-120 mumol of L-phenylalanine/h did not significantly alter plasma leucine kinetics, but increased appearance of plasma phenylalanine and tyrosine. The percentage of phenylalanine and tyrosine appearance that was oxidized increased from 12.1% and 24.4% to 37.3% and 48.0% respectively. In phenylalanine-loaded rats, 72% of plasma tyrosine appearance could be attributed to the conversion of phenylalanine. 4. Whole-body tyrosine oxidation measured from a continuous infusion of either L-[14C]tyrosine or L-[14C]phenylalanine differed by 165%. 5. It can be concluded that, in the post-absorptive state, phenylalanine hydroxylation makes a substantial contribution to the plasma appearance of tyrosine and is significantly increased when phenylalanine is administered. The disposal of excess infused phenylalanine is a result of a greater percentage of plasma phenylalanine being converted into tyrosine and a greater proportion of tyrosine being further oxidized. However...

‣ Effect of glucagon on phenylalanine metabolism and phenylalanine-degrading enzymes in the rat

Brand, Larry M.; Harper, Alfred E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1974 Português
Relevância na Pesquisa
27.118345%
Glucagon administered subcutaneously to rats for 10 days had no significant effect on liver phenylalanine hydroxylase activity, but induced liver dihydropteridine reductase more than twofold. In rats administered a phenylalanine load orally, glucagon treatment stimulated oxidation and depressed urinary phenylalanine excretion. These responses could not be related to an effect of glucagon on hepatic tyrosine–α-oxoglutarate aminotransferase activity. Even in rats with phenylalanine hydroxylase activity depressed to 50% of control values by p-chlorophenylalanine administration, glucagon treatment increased the phenylalanine-oxidation rate substantially. Although hepatic phenylalanine–pyruvate aminotransferase was increased tenfold in glucagon-treated rats, glucagon treatment did not increase urinary excretion of phenylalanine transamination products by rats given a phenylalanine load. Glucagon treatment did not affect phenylalanine uptake by the gut or liver, or the liver content of phenylalanine hydroxylase cofactor. It is suggested that dihydropteridine reductase is the rate-limiting enzyme in phenylalanine degradation in the rat, and that glucagon may regulate the rate of oxidative phenylalanine metabolism in vivo by promoting indirectly the maintenance of the phenylalanine hydroxylase cofactor in its active...

‣ Synthesis and solid state conformation of phenylalanine mimetics constrained in a proline-like conformation

Gardiner, J.; Abell, A.
Fonte: Royal Soc Chemistry Publicador: Royal Soc Chemistry
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
Relevância na Pesquisa
36.759856%
We present the synthesis of five- and six-membered cyclic phenylalanine mimics ( 1, 9, 16, and 17) that are constrained in a proline-like conformation. The five-membered mimetic 16 was prepared by Ring Closing Metathesis (RCM) of diene 15, itself prepared by α-benzylation of the L-methionine derived oxazolidinone 10, followed by oxidative elimination, ring hydrolysis and N-allylation. The six-membered mimetic 1 was prepared by allylating the L-phenylalanine-derived oxazolidinone 5, followed by hydrolysis, N-allylation and RCM. Olefins 1 and 16 were catalytically hydrogenated to give 9 and 17, respectively. The solid state structures of 9 and 16 were determined by X-ray crystallography and their conformations compared with that of 1.; James Gardiner and Andrew D. Abell

‣ Serum phenylalanine in preterm newborns fed different diets of human milk,

Thomaz,Débora M.; Serafin,Paula O.; Palhares,Durval B.; Tavares,Luciana V.M.; Grance,Thayana R.S.
Fonte: Sociedade Brasileira de Pediatria Publicador: Sociedade Brasileira de Pediatria
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2014 Português
Relevância na Pesquisa
36.84501%
Objective:To evaluate phenylalanine plasma profile in preterm newborns fed different human milk diets.Methods:Twenty-four very-low weight preterm newborns were distributed randomly in three groups with different feeding types: Group I: banked human milk plus 5% commercial fortifier with bovine protein, Group II: banked human milk plus evaporated fortifier derived from modified human milk, Group III: banked human milk plus lyophilized fortifier derived from modified human milk. The newborns received the group diet when full diet was attained at 15 ± 2 days. Plasma amino acid analysis was performedon the first and last day of feeding. Comparison among groups was performed by statistical tests: one way ANOVA with Tukey's post-test using SPSS software, version 20.0 (IBM Corp, NY, USA), considering a significance level of 5%.Results:Phenylalanine levels in the first and second analysis were, respectively, in Group I: 11.9 ± 1.22 and 29.72 ± 0.73; in Group II: 11.72 ± 1.04 and 13.44 ± 0.61; and in Group III: 11.3 ± 1.18 and 15.42 ± 0.83 μmol/L.Conclusion:The observed results demonstrated that human milk with fortifiers derived from human milk acted as a good substratum for preterm infant feeding both in the evaporated or the lyophilized form...

‣ Kinetic studies of DNA interstrand crosslink by nitrogen mustard and phenylalanine mustard

Kaminsky, Margaret I.
Fonte: Rochester Instituto de Tecnologia Publicador: Rochester Instituto de Tecnologia
Tipo: Tese de Doutorado
Português
Relevância na Pesquisa
36.759856%
Phenylalanine mustard (PAM) and nitrogen mustard (HN2) are bifunctional alkylating agants which covalently crosslink DNA. Their crosslinking ability forms the basis of their usefulness as anti-cancer drugs since crosslinked DNA cannot replicate and thus the cancers cells cannot reproduce. Despite apparent similarities, the two drugs are known to have important differences. PAM is more effective against cancer and has fewer side effects. In reactions with cell cultures, PAM produces crosslinks more slowly, but the crosslinks are more persistant The experiments reported here offer kinetic explanations for the differences. In vitro time-dependent crosslinking reaction profiles for HN2 and PAM produced using an alkaline ethidium bromide assay for crosslinked DNA are virtually identical to what has been reported in vivo using an alkaline elution method. This suggests that the differences between the two drugs can be explained by purely chemical processes. In particular, the difference in the persistence of PAM and HN2 crosslinks in vivo does not require differences in the rate of enzymatic repair of the two types of lesions since loss of crosslinks in vitro follows the same schedule. A novel modification of the ethidium bromide assay reveals that PAM and HN2 have similar solution stabilities in neutral sodium phosphate buffer. This rules out the possibility that the pharmocological differences between PAM and HN2 are attributable to differential solution stabilities. The dependence of the rate of the crosslinking reaction on drug concentration is linear for both drugs. This confirms previous in vivo studies which suggested that the crosslinking reaction is pseudo first order for drug concentration. The dependence of the reaction rate on the temperature shows that PAM and HN2 have similar activation energies for the crosslinking reaction but PAM has a less favorable steric factor as predicted based on PAM's bulky phenylalanine portion. The crosslinked products for PAM and HN2 were isolated and their rates of decomposition were shown to be first order. PAM crosslinks have a longer half-life and a larger portion of PAM's crosslinks resist decay. These observations may be sufficient to explain the differences between PAM's and HN2's reaction profiles in vivo and in vitro and may be responsible for PAM's greater therapeutic value. A model is proposed to account for PAM's longer half-life and greater fraction of decay-resistant crosslinks.

‣ A Combinatorial library of (alpha)-amide sulfone derivatives of phenylalanine

Hoteling, Andrew
Fonte: Rochester Instituto de Tecnologia Publicador: Rochester Instituto de Tecnologia
Tipo: Tese de Doutorado
Português
Relevância na Pesquisa
36.759856%
The synthesis of a combinatorial library of a-amide sulfone derivatives of phenylalanine was achieved using a solid phase synthesis approach. A multistep reaction sequence was used to introduce two sites of diversity, beginning with phenylalanine as the template attached to ArgoGel-Wang resin. The initial solid phase reaction studies were monitored using nanoprobe NMR and the reaction progress for library synthesis was monitored using a duplicate of one of library members as an analytical control sample. The complete library was evaluated by HPLC-DAD and HPLC-MS analysis of cleaved products. Selected members of the library were characterized using FAB MS/MS and !H NMR. All of the library compounds were synthesized and shown to be the correct desired products. The purity of the library compounds ranged from 3 1 .4% to 88.8% based on area % using HPLC.

‣ Stereocontrolled synthesis of deuterated phenylalanine derivatives through manipulation of an N -phthaloyl protecting group for the recall of stereochemistry. Application in the study of phenylalanine ammonia lyase

Easton, Christopher; Fryer, Nicholas; Kelly, James; Kociuba, Katherine
Fonte: ARKAT Foundation Publicador: ARKAT Foundation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.989404%
The enantiomers of [2-2(H1]phenylalanine and all four stereoisomers of [2,3-2H2]phenylalanine) have been prepared from (S)-phenylalanine through the introduction of a chiral centre onto an N-phthaloyl protecting group for the recall of stereochemistry. Studies of the interaction of these labelled phenylalanines with (S)-phenylalanine ammonia lyase show that both the C-2 and C-3 hydrogens of the product trans-cinnamate undergo exchange with solvent in the presence of the enzyme. The mechanistic implications of this observation are discussed.

‣ Standardization of analytical method to determination of phenylalanine exposure in casein hydrolysates by second derivative spectrophotometry; Padronização de método analítico para avaliação do grau de exposição da fenilalanina em hidrolisados de caseína, por espectrofotometria derivada segunda

Barbosa, Cristiane Márcia da Silva; Morais, Harriman Aley; Silva, Viviane Dias Medeiros; Oliveira, Mônica Cristina de; Silvestre, Marialice Pinto Coelho
Fonte: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas Publicador: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; Artigo Avaliado pelos Pares Formato: application/pdf
Publicado em 01/03/2002 Português
Relevância na Pesquisa
36.759856%
Dietetic formulations for phenylketonurics generally contain free or low phenylalanine protein hydrolysates. Several hydrolytic conditions have been proposed in the literature to increase phenylalanine (Phe) exposure, in order to favor its subsequent removal. The second derivative spectrophotometry (SDS), a fast, simple and low cost analytical method, was used, in this work, for the determination of Phe exposure in different casein hydrolysates, prepared by using papain, and also for the characteriztion of aromatic amino acids. A temperature of 37 ºC, an enzyme:substrate ratio of 4% and a pH 7.5 showed to be the most suitable condition for preparing phenylketonuric diets, since they led to the highest Phe exposure. Concerning the characterization of aromatic amino acids, a good separation of tyrosine (Tyr) and tryptophan (Trp) peaks was obtained in pH 13.0, using the SDS. Moreover, the second derivative spectra of the aromatic amino acids were similar to those of the protein hydrolysates.; Hidrolisados protéicos com baixo teor ou isentos de fenilalanina (Phe) têm sido empregados em formulações para fenilcetonúricos. Várias condições de hidrólise enzimática têm sido propostas na literatura para promover a liberação de Phe e...

‣ Estimativa do teor de fenilalanina em sopas desidratadas instantâneas: importância do nitrogênio de origem não-protéica; Estimation of phenylalanine (Phe) contents in dehydrated soups: significance of non-protein nitrogen

Guimarães, Claudia Passos; Lanfer-Marquez, Ursula Maria
Fonte: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas Publicador: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; Artigo Avaliado pelos Pares Formato: application/pdf
Publicado em 01/09/2005 Português
Relevância na Pesquisa
36.634153%
A análise direta de fenilalanina (Phe) em alimentos com reduzidos teores protéicos destinados a pacientes fenilcetonúricos é difícil, demorada e de alto custo. Emprega-se, geralmente, método indireto baseado na análise do teor protéico bruto, considerando que proteínas naturais contêm ao redor de 4% de Phe. Neste trabalho estimou-se a concentração de Phe em 22 amostras de sopas desidratadas instantâneas, considerando-se os teores de N total, N protéico e não-protéico e de glutamato monossódico (GMS), que foram analisados independentemente. A concentração de proteína bruta (N total multiplicado por fator de conversão adequado) variou entre 6,1 e 21,5 g/100 g amostra, apresentando similaridade com os valores protéicos apresentados nos rótulos das sopas. Os teores protéicos reais foram reduzidos e a concentração de Phe calculada a partir desses dados variou entre 51 e 652 mg/100 g amostra. A concentração de GMS nessas amostras foi considerável, sendo que o N proveniente desse realçador de sabor contribuiu com 2,5 a 47,7% do N total. Concluiu-se que, devido à elevada participação de GMS na formulação das sopas, a estimativa de Phe deve ser precedida de extração prévia de substâncias nitrogenadas não protéicas...

‣ The effect of certain N-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on moloney murine leukaemia virus reverse transcriptase activity

van Zyl,Johann M.; Ariatti,Mario; Hawtrey,Arthur O.
Fonte: South African Journal of Science Publicador: South African Journal of Science
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2010 Português
Relevância na Pesquisa
36.759856%
Moloney murine leukaemia virus (M-MuLV) is a member of the retrovirus family. Its cloned reverse transcriptase (RT), similarly to HIV type 1 reverse transcriptase (HIV-1 RT), exhibits DNA-polymerase and ribonuclease H (RNase H) activities capable of converting the single-stranded retroviral RNA genome into double-stranded DNA. The latter is then integrated into the host chromosome during viral infection. M-MuLV RT is, therefore, an attractive enzyme to help understand mutations in HIV-1 RT and its use in inhibition studies can help facilitate new drug designs. In this study, conjugates consisting of N-trityl derivatives of p-fluoro, p-nitro and p-iodo-DL-phenylalanine were coupled to 8-(6-aminohexyl) amino-adenosine-3',5'-cyclic monophosphate and examined for their effect on DNA synthesis by M-MuLV RT. Synthesis was studied in a system containing poly (rA).oligo d(pT)15 as a template-primer with [³H] dTTP. The iodo-derivative, N-trityl-p-iodo-DL-phenylalanine-8-(6-aminohexyl) amino-adenosine-3',5'-cyclic monophosphate was found to be a very active inhibitor of the RT enzyme (IC50 = 1 µM), while the p-nitro (IC50 = 45 µM) and p-fluoro (IC50 = 65 µM) were weak inhibitors. Further work will be aimed at determining the mode of binding of the N-tritylated conjugates and also of various substituted amino acids and short peptides to M-MuLV RT to elucidate the mechanisms of inhibition.