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21.
Synthesis and structural characterization of bioactive peptide conjugates using thioether linkage approaches. 总被引:1,自引:0,他引:1
Gbor Mez Marilena Manea Annamria Jakab Bence Kapuvri Szilvia Bsze Gitta Schlosser Michael Przybylski Ferenc Hudecz 《Journal of peptide science》2004,10(12):701-713
Applications of cysteine-insertion and thioether linkage approaches to the preparation of a number of bioactive peptide conjugates are reported. Peptides containing epitopes from (i) herpes simplex virus type 1 glycoprotein D, (ii) a specific N-terminal beta-amyloid epitope recognized by therapeutically active antibodies, and (iii) a GnRH-III peptide from sea lamprey with antitumour activity, were elongated with Cys residues and attached to a chloroacetylated tetratuftsin derivative carrier via a thioether linkage either directly, or by insertion of a spacer. The structures and molecular homogeneity of all the peptide conjugates were ascertained by HPLC, MALDI and electrospray mass spectrometry. The use of a spacer such as an oligoglycine or GFLG-tetrapeptide gave an increased yield in the conjugation reaction and enhanced reaction rates. In the formation of cysteinyl-thioether linkages, it was found that the position of flanking Cys residues markedly influenced the conjugation reaction and the formation of intermolecular epitope disulfide-dimers. C-terminal Cys residues gave thioether conjugates with significantly diminished epitope-dimerization, while Cys at the N-terminal caused rapid disulfide-dimerization, thereby preventing efficient conjugation. 相似文献
22.
I Varga C Jakab N Szücs A Patócs M Tóth R Kiss E Gláz K Rácz 《Hormones et métabolisme》2003,35(7):421-426
The aim of this study was to examine and compare the potential usefulness of plasma and salivary 6beta-hydroxycortisol measurements for assessing adrenocortical activity in patients with adrenocortical adenomas. Plasma and salivary cortisol as well as 6beta-hydroxycortisol determinations were performed by radioimmunoassay after extraction with ethyl acetate followed by chromatographic separation using a modified paper chromatographic system. Samples were obtained from 36 control subjects and 37 patients with non-hyperfunctioning adrenocortical adenomas in the morning at 8 a.m. after a low-dose of dexamethasone and after stimulation with synthetic depot ACTH. Basal and post-dexamethasone hormone levels were also measured in plasma and salivary samples of 4 patients with Cushing's syndrome from adrenal adenomas. In the baseline state, patients with non-hyperfunctioning adrenocortical adenomas had significantly higher plasma and salivary 6beta-hydroxycortisol levels (mean+/-SE, 79.0+/-7 and 17.1+/-2.2 ng/dl, respectively) compared to those measured in controls (62.0+/-4 and 7.7+/-0.6 ng/dl, respectively), whereas baseline plasma and salivary cortisol levels (9.6+/-0.5 microg/dl and 342+/-39 ng/dl, respectively) were similar to those measured in the control group (9.9+/-0.4 microg/dl and 366+/-24 ng/dl, respectively). In all groups, the changes in plasma and salivary 6beta-hydroxycortisol concentrations after dexamethasone suppression and ACTH stimulation were similar to the changes in plasma and salivary cortisol levels, although the differing ratios of 6betaOHF to cortisol indicated potentially important variations in the induction of 6beta-hydroxylase activity between the three groups. In patients with Cushing's syndrome, baseline plasma and salivary 6beta-hydroxycortisol concentrations (754+/-444 and 104+/-88 ng/dl, respectively) were more markedly increased than plasma and salivary cortisol levels (24.8+/-6.7 microg/dl and 1100+/-184 ng/dl, respectively), and all remained non-suppressible after dexamethasone administration. These results suggests that plasma and salivary 6beta-hydroxycortisol determinations may precisely detect not only overt increases of cortisol secretion in patients with Cushing's syndrome but also mild glucocorticoid overproduction presumably present in patients with non-hyperfunctioning adrenocortical tumors. 相似文献
23.
Nóra Kutszegi ágnes F. Semsei András Gézsi Judit C. Sági Viktória Nagy Katalin Csordás Zsuzsanna Jakab Orsolya Lautner-Csorba Krisztina Míta Gábor Gábor T. Kovács Dániel J. Erdélyi Csaba Szalai 《PloS one》2015,10(10)
L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. 相似文献
24.
Genetic and phenotypic variation in central and northern European populations of Aedes (Aedimorphus) vexans (Meigen, 1830) (Diptera,Culicidae)
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Ljubinka Francuski Vesna Milankov Jasmina Ludoški Bosiljka Krtinić Jan O. Lundström Gábor Kemenesi Jakab Ferenc 《Journal of vector ecology》2016,41(1):160-171
The floodwater mosquito Aedes vexans can be a massive nuisance in the flood plain areas of mainland Europe, and is the vector of Tahyna virus and a potential vector of Dirofilaria immitis. This epidemiologically important species forms three subspecies worldwide, of which Aedes vexans arabiensis has a wide distribution in Europe and Africa. We quantified the genetic and phenotypic variation in Ae. vexans arabiensis in populations from Sweden (northern Europe), Hungary, and Serbia (central Europe). A landscape genetics approach (FST, STRUCTURE, BAPS, GENELAND) revealed significant differentiation between northern and southern populations. Similar to genetic data, wing geometric morphometrics revealed two different clusters, one made by Swedish populations, while another included Hungarian and Serbian populations. Moreover, integrated genetic and morphometric data from the spatial analysis suggested groupings of populations into three clusters, one of which was from Swedish and Hungarian populations. Data on spatial analysis regarding an intermediate status of the Hungarian population was supported by observed Isolation‐by‐Distance patterns. Furthermore, a low proportion of interpopulation vs intrapopulation variance revealed by AMOVA and low‐to‐moderate FST values on a broader geographical scale indicate a continuous between‐population exchange of individuals, including considerable gene flow on the regional scale, are likely to be responsible for the maintenance of the observed population similarity in Aе. vexans. We discussed data considering population structure in the light of vector control strategies of the mosquito from public health importance. 相似文献
25.
Palaeoclimatic signals and anthropogenic disturbances from the peatbog at Nagybárkány (North Hungary) 总被引:1,自引:1,他引:0
Gusztáv Jakab Péter Majkut Imola Juhász Sándor Gulyás Pál Sümegi Tünde Törőcsik 《Hydrobiologia》2009,631(1):87-106
Investigation of a small peatbog in northern Hungary provides a late Quaternary record of vegetation development effected
by climatic changes and anthropogenic disturbances. The aim of this study was to separate climatic signals from the development
of a continental eutrophic peatland with the use of plant macrofossil analysis. The development of water catchment is reconstructed
using pollen and geochemical analyses. The formation of the lakebed can be traced back to the Late Glacial. A higher water
level with oligotrophic conditions can be existed from the Late Glacial to middle Holocene, when the reed beds covered a small
area only. This was followed by a hiatus spanning ca. 4400 years, caused by peat cutting during the Imperial Age. The water
level decreased and the water quality was more eutrophic. A reed bed evolved around the lake. Terrestrialization started with
a bulrush floating mat phase at the close of the árpádian Age, ca. cal yr AD 1400. The initiation of the Sphagnum-bog underwent similar phases as in the other Hungarian peatbogs. Although remarkable anthropogenic disturbances can be reconstructed
in the development of the peatbog, some climatic effects and authogenic processes might be separated by palaeoecological analyses.
Guest editors: K. Buczkó, J. Korponai, J. Padisák & S. W. Starratt
Palaeolimnological Proxies as Tools of Environmental Reconstruction in Fresh Water 相似文献
26.
27.
Anna-Mária Cserg? Szilárd Nemes Dan Gafta László Demeter Sámuel Jakab 《Plant Ecology》2009,203(2):229-242
We modelled the effect of habitat heterogeneity on the abundance of the submediterranean Saponaria bellidifolia, a red list species in Romania. The study was designed at two scales: 100 and 0.5 m2. At larger scale, generalized additive models and canonical correspondence analysis were used to model the density of ramets,
whereas at microscale, binomial logistic regression was employed to model the species’ occurrence. S. bellidifolia abundance responded sensitively to habitat type (classified as “grassy”, “rocky” and “scree”), rather than to microclimatic
variables. At both scales, habitat type was the best predictor of ramet abundance, followed by slope and vegetation cover.
At 0.5 m2, soil depth was also a good predictor of species occurrence. The data revealed that screes are the most suitable habitats
for hosting relatively large populations of this rare species, because of occasional natural disturbances and presumably lower
interspecific competition. 相似文献
28.
Synthetic Analogues of Conantokin-G: NMDA Antagonists Acting Through a Novel Polyamine-Coupled Site 总被引:3,自引:2,他引:1
Li-Ming Zhou Gyorgyi I. Szendrei Linda H. Fossom †Maria-Luisa Maccecchini Phil Skolnick Laszlo Otvos Jr. 《Journal of neurochemistry》1996,66(2):620-628
Abstract: Conantokin-G (con-G) is a 17-amino-acid polypeptide that acts as an N-methyl-d -aspartate (NMDA) antagonist. This action has been attributed to a specific but noncompetitive inhibition of the positive modulatory effects of polyamines at NMDA receptors. Con-G possesses several unusual structural features, including five γ-carboxyglutamate (Gla) residues and a high degree of helicity in aqueous media. Previous structure-activity studies indicated that one or more Gla residues are necessary for NMDA antagonist activity. Con-G analogues were synthesized with alanine (Ala), serine (Ser), and phosphoserine substituted for Gla to assess the contribution of individual Gla residues to biological activity and secondary structure. Replacement of Gla in positions 3 and 4 resulted in polypeptides with markedly reduced and no NMDA antagonist actions, respectively. In contrast, Gla residues in positions 7, 10, and 14 are not required for NMDA antagonist actions because the potencies of con-G analogues containing Ser7, Ser10, Ala14, and Ser14 to inhibit spermine-stimulated [3H]MK-801 binding are similar to the parent peptide. Moreover, the Ala7 derivative of con-G was about fourfold more potent than the parent peptide both as an inhibitor of spermine-stimulated increases in [3H]MK-801 binding (IC50 of ~45 nM) and in reducing NMDA-stimulated increases in cyclic GMP levels (IC50 of ~77 nM) in cerebellar granule cell cultures. Although con-G and its analogues assumed mixtures of 310 and α-helices, no clear-cut relationship was evinced between the NMDA antagonist properties of these peptides and the degree of helicity they assumed in aqueous solutions. Together with the inability of con-G to affect 5,7-dichloro[3H]kynurenic acid, [3H]CGP-39653, and [3H]ifenprodil binding, these data are consistent with the hypothesis that this polypeptide acts at a unique, polyamine-associated site on NMDA receptors. 相似文献
29.
MariaLisa Garavaglia Silvia Dopinto Markus Ritter Johannes Fürst Stefano Saino Fabiana Guizzardi Martin Jakab Claudia Bazzini Valeria Vezzoli Silvia Dossena Simona Rodighiero Chiara Sironi Guido Bottà Giuliano Meyer Robert M Henderson Markus Paulmichl 《Cellular physiology and biochemistry》2004,14(4-6):231-240
The plasma membrane is a highly dynamic cell-barrier if the nature and distribution of its constituents are considered. Ion channels are embedded in these double lipid bilayers, which modulate their 3D-structures. The structure modulations by the lipid bilayer can assume such a degree that channel activation depends on them, as was shown for the KcsA potassium channel. Here we show that the cation-over-anion selectivity of reconstituted ICln channels can be varied by the thickness of a bilayer build of phosphatidylcholines. The shorter the acyl-chains and therefore the thinner the bilayers of the membrane are, the more potassium selective the channels are. In contrast, the longer the acyl-chains and therefore the thicker the membranes are, the more chloride selective the channels become. 相似文献
30.