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81.
Construction of a 'unigene' cDNA clone set by oligonucleotide fingerprinting allows access to 25 000 potential sugar beet genes 总被引:1,自引:0,他引:1
82.
Two artificial transaminases were assembled by linking a pyridoxamine derivative within an engineered fatty acid binding protein. The goal of mimicking a native transamination site by stabilizing a cationic pyridoxamine ring system was approached using two different strategies. First, the scaffold of intestinal fatty acid binding protein (IFABP) was tailored by molecular modeling and site-directed mutagenesis to position a carboxylate group close to the pyridine nitrogen of the cofactor. When these IFABP mutants (IFABP-V60C/L38K/E93E and -V60C/E51K/E93E) proved to be unstable, a second approach was explored. By N-methylation of the pyridoxamine, a cationic cofactor was created and tethered to Cys60 of IFABP-V60C/L38K and -V60C/E51K; this latter strategy had the effect of permanently installing a positive charge on the cofactor. These chemogenetic assemblies catalyze the transamination between alpha-ketoglutarate and various amino acids with enantioselectivities of up to 96% ee. The pH profile of the initial rates is bell shaped and similar to native aminotransferases. The k(cat) values and the turnover numbers for these new constructs are the highest achieved to date in our system. This success was only made possible by the unique flexibility of the underlying enzyme design concept employed, which permits full control of both the protein scaffold and the catalytically active group. 相似文献
83.
Herling AW Schwab D Burger HJ Maas J Hammerl R Schmidt D Strohschein S Hemmerle H Schubert G Petry S Kramer W 《Biochimica et biophysica acta》2002,1569(1-3):105-110
Chlorogenic acid derivatives are potent inhibitors of hepatic glucose production by inhibition of the glucose-6-phosphate translocase component of the hepatic glucose-6-phosphatase system. The pharmacological proof of concept was clearly demonstrated during i.v. infusion of potent derivatives (S 4048, S 3483) in rats. However, the blood glucose lowering effect of S 4048 after bolus i.v. injection lasted only 60-90 min. Plasma clearance of S 4048 was very high, and the parent compound was rapidly and efficiently excreted into the bile of Wistar and GY/TR(-) rats, indicating that mrp-2 was not involved in this hepatobiliary elimination process. About 72% of the total administered radioactivity appeared in the bile within 20 min after i.v. bolus injection of the radiolabeled analogue [(3)H]S 1743 in a Wistar rat. However, in GY/TR(-) rats the dicarboxylic analogue of S 4048, S 3025, was cleared from the plasma less rapidly than its parent compound and its biliary elimination was comparatively low. In contrast, S 3025 exhibited comparable pharmacokinetics and biliary elimination profile as S 4048 in Wistar rats, suggesting that biliary elimination of S 3025 is facilitated by mrp-2, functionally absent in GY/TR(-) rats. Targeting to mrp-2 resulted in a significantly prolonged reduction of blood glucose levels in GY/TR(-) rats after i.v. bolus administration of S 3025. 相似文献
84.
Schirmer RH Coulibaly B Stich A Scheiwein M Merkle H Eubel J Becker K Becher H Müller O Zich T Schiek W Kouyaté B 《Redox report : communications in free radical research》2003,8(5):272-275
Methylene blue has intrinsic antimalarial activity and it can act as a chloroquine sensitizer. In addition, methylene blue must be considered for preventing methemoglobinemia, a serious complication of malarial anemia. As an antiparasitic agent, methylene blue is pleiotropic: it interferes with hemoglobin and heme metabolism in digestive organelles, and it is a selective inhibitor of Plasmodium falciparum glutathione reductase. The latter effect results in glutathione depletion which sensitizes the parasite for chloroquine action. At the Centre de Recherche en Santé de Nouna in Burkina Faso, we study the combination of chloroquine with methylene blue (BlueCQ) as a possible medication for malaria in endemic regions. A pilot study with glucose-6-phosphate dehydrogenase-sufficient adult patients has been conducted recently. 相似文献
85.
86.
A novel pathway for mineralization of the thiocarbamate herbicide molinate by a defined bacterial mixed culture 总被引:1,自引:0,他引:1
Barreiros L Nogales B Manaia CM Ferreira AC Pieper DH Reis MA Nunes OC 《Environmental microbiology》2003,5(10):944-953
A bacterial mixed culture able to mineralize molinate was established, through enrichment, using mineral medium with molinate as the only carbon, nitrogen and energy source. The combination of five cultivable isolates, purified from the enrichment culture, permitted the reconstitution of a degrading consortium. Both enrichment and defined cultures were able to mineralize molinate without accumulation of degradation products by the end of the growth. Among the five isolates constituting the defined mixed culture, an actinomycete, strain ON4, was essential for biodegradation, being involved in the cleavage of the thioester bond of molinate, the initial step of the degradation pathway. Isolate ON4 was able to grow on molinate at concentrations below 2 mM, with the accumulation of ethanethiol and diethyl disulphide. These sulphur compounds were toxic to strain ON4 when accumulating at higher concentrations. However, this inhibitory effect was avoided by the presence of other members of the mixed culture, out of which isolates ON1 and ON2 were observed to consume ethanethiol and diethyl disulphide. In this way, interactions among defined mixed culture members involve metabolic and detoxifying association. 相似文献
87.
Zeis B Becher B Lamkemeyer T Rolf S Pirow R Paul RJ 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2003,134(2):243-252
The process of oxygen-dependent hemoglobin induction in Daphnia magna was studied over an 11-day period of hypoxia (ambient oxygen partial pressure: 3 kPa). Along with the increase of hemoglobin concentration in the hemolymph, hemoglobin became the dominant protein fraction in gel filtration experiments using extracts of whole animals. The size of the native aggregates was constant. However, subunit composition depended on the duration of hypoxia: the pattern of predominantly expressed subunits under hypoxia deviated from that of normoxic individuals. The varying degree of hypoxic induction for different hemoglobin subunits was confirmed by autoradiography. Along with changes in hemoglobin subunit composition, oxygen affinity of the respiratory protein increased. The dynamics of the hemoglobin induction process was analysed. Newly synthesized hemoglobin can be detected within 18 h after the onset of hypoxia. A marked increase in hemoglobin concentration is evident from the third day of hypoxia, and a steady state of hemoglobin concentration is reached within 11 days. The changes of hemoglobin subunit expression in response to hypoxia form the structural basis for the observed adjustments of hemoglobin function leading to enhanced oxygen transport at low ambient oxygen concentrations. 相似文献
88.
89.
Oligonucleotides incorporating 8-aza-7-deazapurin-2,6-diamine (pyrazolo[3,4-d]pyrimidin-4,6-diamine) nucleoside 2a or its 7-bromo derivative 2b show enhanced duplex stability compared to those containing dA. While incorporation of 2a opposite dT increases the Tm value only slightly, the 7-bromo compound 2b forms a very stable base pair which is as strong as the dG-dC pair. Compound 2b shows a similar base discrimination in duplex DNA as dA. The base-modified nucleosides 2a,b have a significantly more stable N-glycosylic bond than the rather labile purin-2,6-diamine 2′-deoxyribonucleoside 1. Base protection with acyl groups, with which we had difficulties in the case of purine nucleoside 1, was effective with pyrazolo[3,4-d]-pyrimidine nucleosides 2a,b. Oligonucleotides containing 2a,b were obtained by solid phase synthesis employing phosphoramidite chemistry. Compound 2b harmonizes the stability of DNA duplexes. Their stability is no longer dependent on the base pair composition while they still maintain their sequence specificity. Thus, they have the potential to reduce the number of mispairs when hybridized in solution or immobilized on arrays. 相似文献
90.
The fluorescence and the base pairing properties of 8-aza-7-deaza-2'-deoxyisoinosine (1) are described and compared with those of 2'-deoxyisoinosine (2). The corresponding phosphoramidites (11, 12) are synthesized using the diphenylcarbamoyl (DPC) residue for the 2-oxo group protection. The nucleosides 1 and 2 base pair with 2'-deoxy-5-methylisocytidine in DNA duplexes with antiparallel chain orientation and with 2'-deoxycytidine in a parallel DNA. These base pairs are less stable than the canonical dA-dT pair and that of 2'-deoxyinosine (4) with 2'-deoxycytidine. The fluorescence of the nucleosides 1 and 2 is quenched (approximately 95%) in duplex DNA. The residual fluorescence is used to determine the Tm-values, which are found to be the same as determined UV-spectrophotometrically. 相似文献