排序方式: 共有147条查询结果,搜索用时 31 毫秒
41.
Mittendorf J Kunisch F Matzke M Militzer HC Schmidt A Schönfeld W 《Bioorganic & medicinal chemistry letters》2003,13(3):433-436
A series of novel beta-amino acids has been synthesized and tested for their in vitro antifungal activity against Candida albicans. A steep SAR was observed. beta-Amino acid 21 (BAY 10-8888/PLD-118) revealed the most favourable activity-tolerability profile and was selected for clinical studies as a novel antifungal for the oral treatment of yeast infections. 相似文献
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Siebert HC Lü SY Frank M Kramer J Wechselberger R Joosten J André S Rittenhouse-Olson K Roy R von der Lieth CW Kaptein R Vliegenthart JF Heck AJ Gabius HJ 《Biochemistry》2002,41(30):9707-9717
Structural analysis of minimally sized lectins will offer insights into fundamentals of intermolecular recognition and potential for biomedical applications. We thus moved significantly beyond the natural limit of lectin size to determine the structure of synthetic mini-lectins in solution, their carbohydrate selectivity and the impact of ligand binding on their conformational behavior. Using three disaccharide (Thomsen-Friedenreich antigen; Gal beta 1,3GalNAc alpha 1,R)-binding pentadecapeptides without internal disulfide bridges as role models, we successfully tested a combined strategy with different techniques of NMR spectroscopy, electrospray ionization mass spectrometry, and molecular modeling. In solution, the peptides invariably displayed flexibility with rather limited restrictions, shown by NMR experiments including nearly complete resonance assignments and molecular dynamics simulations. The occurrence of aromatic/nonpolar amino acids in the sequence did not lead to formation of a hydrophobic core known from microbial chitinase modules. Selectivity of disaccharide binding was independently observed by mass spectrometry and NMR analysis. Specific ligand interaction yielded characteristic NMR signal alterations but failed to reduce conformational flexibility significantly. We have thereby proven effectiveness of our approach to analyze even low-affinity interactions (not restricted to carbohydrates as ligands). It will be useful to evaluate the impact of rational manipulation of lead peptide sequences. 相似文献
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Tumor targeting of glycoconjugated antineoplastic agents is a strategy currently under investigation for cancer chemotherapy. We have synthesized the glucosides and galactosides of the clinically established drug hydroxyurea and of mesylglycol, the reactive moiety of the anticancer drug busulfan. Glycosides of hydroxyurea were obtained by carbamoylation of hydroxylamine glycosides. The glycosides of mesylglycol were synthesized by mesylation of protected glycol glycosides. All compounds were characterized by detailed 1H and 13C NMR analysis. 相似文献
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Neural Induction of the Blood–Brain Barrier: Still an Enigma 总被引:5,自引:0,他引:5
1. The study of the blood–brain barrier and its various realms offers a myriad of opportunities for scientific exploration. This review focuses on two of these areas in particular: the induction of the blood–brain barrier and the molecular mechanisms underlying this developmental process.2. The creation of the blood–brain barrier is considered a specific step in the differentiation of cerebral capillary endothelial cells, resulting in a number of biochemical and functional alterations. Although the specific endothelial properties which maintain the homeostasis in the central nervous system necessary for neuronal function have been well described, the inductive mechanisms which trigger blood–brain barrier establishment in capillary endothelial cells are unknown.3. The timetable of blood–brain barrier formation is still a matter of debate, caused largely by the use of varying experimental systems and by the general difficulty of quantitatively measuring the degree of blood–brain barrier tightness. However, there is a general consensus that a gradual formation of the blood–brain barrier starts shortly after intraneural neovascularization and that the neural microenvironment (neurons and/or astrocytes) plays a key role in inducing blood–brain barrier function in capillary endothelial cells. This view stems from numerous in vitro experiments using mostly cocultures of capillary endothelial cells and astrocytes and assays for easily measurable blood–brain barrier markers. In vivo, there are great difficulties in proving the inductive influence of the neuronal environment. Also dealt with in this article are brain tumors, the least understood in vivo systems, and the induction or noninduction of barrier function in the newly established tumor vascularization.4. Finally, this review tries to elucidate the question concerning the nature of the inductive signal eliciting blood–brain barrier formation in the cerebral microvasculature. 相似文献
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Alternative migration routes of Ascaris suum in the pig 总被引:1,自引:0,他引:1
Boes J Slotved HC Murrell KD Eriksen L Roepstorff A Nansen P Agergaard N 《The Journal of parasitology》2002,88(1):180-183
Experiments were conducted to investigate possible alternative routes of extraintestinal migration of Ascaris suum larvae in the pig. Pigs were infected with A. suum via injection of newly hatched larvae into cecal veins (i.v.), into cecal lymph nodes (LN), or intraperitoneally (i.p.), and control animals were inoculated orally with infective eggs (p.o.). Two pigs per inoculation route were necropsied on days 1, 4, and 13 postinoculation. The numbers of liver lesions and the percentage of larvae recovered was considerably greater in pigs inoculated i.v. or p.o. on each necropsy day. However, irrespective of inoculation route, at least a proportion of larvae passed through the livers and were able to complete migration to the small intestine by day 13. The results indicate that larval penetration of the intestinal wall is not necessary for liver-lung migration and that passage through the liver may be favorable for migrating A. suum larvae, although a delayed arrival in the small intestine cannot be ruled out for larvae following alternative routes. 相似文献
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Huber C Marschallinger J Tempfer H Furtner T Couillard-Despres S Bauer HC Rivera FJ Aigner L 《Cellular physiology and biochemistry》2011,28(5):793-804
Neural stem and progenitor cells serve as a reservoir for new neurons in the adult brain throughout lifetime. One of the critical steps determining the net production of new neurons is neural progenitor proliferation, which needs to be tightly controlled. Since inflammation has detrimental effects on neurogenesis and the 5-lipoxygenase/leukotriene pathway is involved in inflammatory processes, we investigated the effects of leukotrienes and montelukast, a small molecule inhibitor of the leukotriene receptors CysLT(1)R and GPR17, on neural stem and progenitor cell proliferation. We demonstrate expression of the leukotriene receptor GPR17 by neural progenitors and by neural stem cells. Stimulation with excess amounts of leukotrienes did not affect progenitor proliferation, whereas blockade of GPR17 with montelukast strongly elevated neural stem and progenitor proliferation, while maintaining their differentiation fate and potential. This effect was associated with increased ERK1/2 phosphorylation suggesting an involvement of the EGF signaling cascade. Based on our results, montelukast and the inhibition of the 5-LOX pathway might be potent candidates for future therapies employing neurogenesis to promote structural and functional improvement in neurodegeneration, neuropsychiatric disease and ageing. 相似文献
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Troponin elevation in acute ischemic stroke (TRELAS) - protocol of a prospective observational trial
Jan F Scheitz Hans-Christian Mochmann Christian H Nolte Karl G Haeusler Heinrich J Audebert Peter U Heuschmann Ulrich Laufs Bernhard Witzenbichler Heinz-Peter Schultheiss Matthias Endres 《BMC neurology》2011,11(1):98
Background
Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup. 相似文献50.
Stein P Weber M Prüfer S Schmid B Schmitt E Probst HC Waisman A Langguth P Schild H Radsak MP 《PloS one》2011,6(11):e27911