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461.
Kostas K. Barlos Dimitrios Gatos Zoe Vasileiou Kleomenis Barlos 《Journal of peptide science》2010,16(4):200-211
Human gene 2 relaxin (RLX) is a member of the insulin superfamily and is a multi‐functional factor playing a vital role in pregnancy, aging, fibrosis, cardioprotection, vasodilation, inflammation, and angiogenesis. RLX is currently applied in clinical trials to cure among others acute heart failure, fibrosis, and preeclampsia. The synthesis of RLX by chemical methods is difficult because of the insolubility of its B‐chain and the required laborious and low yielding site‐directed combination of its A (RLXA) and B (RLXB) chains. We report here that oxidation of the Met25 residue of RLXB improves its solubility, allowing its effective solid‐phase synthesis and application in random interchain combination reactions with RLXA. Linear Met(O)25‐RLX B‐chain (RLXBO) reacts with a mixture of isomers of bicyclic A‐chain (bcRLXA) giving exclusively the native interchain combination. Applying this method Met(O)25‐RLX (RLXO) was obtained in 62% yield and was easily converted to RLX in 78% yield, by reduction with ammonium iodide. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
462.
Evidence for multiple functional active oxidants in cytochrome P450-catalyzed reactions was previously obtained in this laboratory with mutants in which proton delivery was perturbed by replacement of the highly conserved threonine residue in the active site by alanine, thus apparently interfering with the conversion of the peroxo-iron to the hydroperoxo-iron and the latter to the oxenoid-iron species. These enzymes have now been employed to examine the reaction in which cytochrome P450 in liver microsomes is known to effect ipso-substitution, the elimination of p-substituents in phenols to yield hydroquinone. As shown with purified NH(2)-truncated cytochromes in a reconstituted enzyme system, the reaction exhibits an absolute requirement for cytochrome P450 and NADPH-cytochrome P450 reductase. Under optimal conditions truncated cytochrome P450 2E1 is active with 10 of the p-substituted phenols examined. Of particular interest, the corresponding cytochrome with threonine-303 replaced by alanine is from 1.5- to 50-fold higher in activity with the p-chloro, -bromo, -nitro, -cyano, -hydroxymethyl, -formyl, and -acetyl derivatives, and the reaction with the p-benzoyl, -methyl, and -t-butyl compounds is catalyzed by the mutant enzyme only. The results implicate the hydroperoxo-iron species as an electrophilic active oxidant in cytochrome P450-catalyzed aromatic ipso-substitution. 相似文献
463.
The synthesis of new aminodeoxy and amino acid nucleosides of talose and mannose is described. The unusual conformation of these hexosylpurines revealed by n.m.r. spectroscopy is reported, as well as the unexpected results of some substitution reactions. 相似文献
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Vassiliki Kati Kostas Poirazidis Marc Dufrêne John M. Halley Giorgos Korakis Stefan Schindler Panayotis Dimopoulos 《Biodiversity and Conservation》2010,19(6):1585-1597
In this paper, we present a novel approach for using ecological heterogeneity in reserve design. We measured five ecological
heterogeneity indices (EHI) and we used a database of six biological groups (woody plants, orchids, orthopterans, aquatic and terrestrial herpetofauna
and passerine birds) across 30 sites in a Mediterranean reserve (Greece). We found that all the five EHI were significantly related to the overall species richness and to the species richness of woody plants and birds. Two indices,
measuring vertical vegetation complexity (1/D) and horizontal heterogeneity of landcover types (SIDI) in terms of Simpson’s index, predicted well overall species richness and had significantly higher values inside the complementary
reserve networks designed after five of the six biological groups. We compared five methods of forming reserve networks. The
method of ecological heterogeneity (selecting those sites with the greatest 1/D and then SIDI) was less efficient (non-significantly) than the species-based methods (scoring and complementary networks) but significantly
more efficient than the random method (randomly selected network). We also found that the method of complementary ecological
heterogeneity (selecting those sites where each EHI had its maximum value) was not that efficient, as it did not differ significantly from the random method. These results underline
the potential of the ecological heterogeneity method as an alternative tool in reserve design. 相似文献
467.
Dr. Kostas Alexopoulos Prof. John Matsoukas T. Tsehos P. Roumelioti T. Mavromoustakos K. Holada 《Amino acids》1998,15(3):211-220
Summary Thrombin, the most potent physiological platelet agonist interacts with cells through a specific G protein-coupled receptor which has been cloned and sequenced. Synthetic thrombin receptor peptides (TRAPS) comprising the first 5 amino acids (SFLLR and SFLLR-NH2) of the new N-terminus tethered ligand of the thrombin receptor that is generated by thrombin's proteolytic activity were found to cause full platelet aggregation. During the screening of novel thrombin receptor derived non-peptide mimetics in the platelet aggregation assay we found that 1-phenylacetyl-4-(6-guanidohexanoyl)-piperazine (1) and 1-(6-guanidohexanoyl)-4-(phenylacetylamidomethyl)-piperidine (2) exertedin vitro antagonist activities (56% and 40% correspondingly) as it is depicted by the platelet aggregation assay. Using Molecular Modeling, the synthetic compounds were overlayed with SFFLR. All three superimposed low energy structures had Phe and Arg aminoacids in spatial close proximity. The superimposition results revealed that1 resembled more the stereoelectronic environment of SFLLR than2. This difference may be related to their different antagonist efficacy. 相似文献
468.
Apostolis Papapostolou Kostas Spengos Irene Fylaktou Myrto Poulou Ilias Gountas Sophia Kitsiou-Tzeli Emmanuel Kanavakis Maria Tzetis 《Gene》2014
ALOX5AP (5-lipoxygenase) has been recognized as a susceptibility gene for stroke. Using a case–control design, the whole coding and adjoining intronic regions of ALOX5AP were sequenced to study the role of SNPs and their interplay with other risk factors in Greek patients with stroke. Patients (n = 213) were classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Their mean age of was 58.9 ± 14.64, comprising 145 males. The control group consisted of 210 subjects, ethnicity, sex and age matched, with no stroke history. Risk factors (hyperlipidemia, hypertension, atrial fibrillation, migraine, CAD, diabetes, smoking and alcohol consumption) were assessed as confounding factors and comparisons were done using logistic regression analysis. SNPs rs4769055, rs202068154 and rs3803277 located in intronic regions of the gene and according to in silico programs EX_SKIP and HSF possibly affecting splicing of exons 1 and 2 of ALOX5AP, showed significantly different frequencies between patients and controls. The genotype frequencies of rs4769055: AA, of rs202068154: AC and of rs3803277: CA were significantly higher (p < 0.001, 0.058) in controls than in patients. The results were indicative of a protective role of the three SNPs either in homozygosity or heterozygosity for MAF and more specifically rs3803277: CA/AA genotypes were protective against SVO stroke subtype. 相似文献
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Theocharis Berris Kostas Perisinakis Antonios E. Papadakis John Damilakis 《Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)》2013,29(3):312-322
The aim of the current study was to compare the film method against the method based on a new CT slice detector in assessing geometric efficiency (GE) of x-ray beams utilized by a multi-detector CT (MDCT) scanner. Measurements of GE were performed using radiographic films and a solid state CT slice detector for all beam qualities, collimations and focal spot sizes available on an MDCT scanner. Repeatability of GE measurements was assessed. The radiographic film and the solid state detector methods were compared to each other in regard to efficacy in measuring free-in-air GE. The values of GE determined using the radiographic film method were found to range between 48.5% and 90.6%. Differences between values obtained with the radiographic film method and corresponding values obtained with the solid state detector were less than 10% exceeding 5% for only one case. Both methods show that wide beams have higher GE values compared to thin ones. The use of large instead of small focal spot was found to deteriorate GE values by up to 23.1%. Beam quality did not seem to influence GE of the various collimations. When thin beam collimations are employed, a considerable amount of the radiation is wasted for non-imaging purposes. Both film and solid state probe methods are capable of measuring GE of thin as well as wide collimations. The solid state detector is the easiest to use, however its usefulness is reduced by the fact that it cannot measure dose profiles of beam collimations available for step-and-shoot mode of operation. 相似文献