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排序方式: 共有202条查询结果,搜索用时 15 毫秒
141.
Marco van Eijk Tineke Voorn-Brouwer Saskia S. Scheij Arthur J. Verhoeven Rolf G. Boot Johannes M.F.G. Aerts 《FEBS letters》2010,584(14):3165-3169
Human phagocyte-specific chitotriosidase is part of innate immunity and shows anti-fungal activity towards chitin-containing fungi. We investigated the effect of stimulation of the C-type lectin receptor dectin-1 by β-1,3-glucan (curdlan) on chitotriosidase expression and release by human phagocytes. We observed that curdlan triggers chitotriosidase release from human neutrophils. In addition, we show that curdlan impairs chitotriosidase induction in monocytes. Finally, curdlan temporarily induces chitotriosidase in enzyme-expressing monocyte-derived macrophages, followed by reduction of chitotriosidase expression after prolonged stimulation. These data on regulation of phagocyte-specific chitotriosidase following curdlan recognition support an important role of chitotriosidase in the elimination of chitin-containing pathogens. 相似文献
142.
Torrado A Lamas C Agejas J Jiménez A Diaz N Gilmore J Boot J Findlay J Hayhurst L Wallace L Broadmore R Tomlinson R 《Bioorganic & medicinal chemistry》2004,12(20):5277-5295
A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression. 相似文献
143.
Crystal structures of allosamidin derivatives in complex with human macrophage chitinase 总被引:4,自引:0,他引:4
Rao FV Houston DR Boot RG Aerts JM Sakuda S van Aalten DM 《The Journal of biological chemistry》2003,278(22):20110-20116
The pseudotrisaccharide allosamidin is a potent family 18 chitinase inhibitor with demonstrated biological activity against insects, fungi, and the Plasmodium falciparum life cycle. The synthesis and biological properties of several derivatives have been reported. The structural interactions of allosamidin with several family 18 chitinases have been determined by x-ray crystallography previously. Here, a high resolution structure of chitotriosidase, the human macrophage chitinase, in complex with allosamidin is presented. In addition, complexes of the allosamidin derivatives demethylallosamidin, methylallosamidin, and glucoallosamidin B are described, together with their inhibitory properties. Similar to other chitinases, inhibition of the human chitinase by allosamidin derivatives lacking a methyl group is 10-fold stronger, and smaller effects are observed for the methyl and C3 epimer derivatives. The structures explain the effects on inhibition in terms of altered hydrogen bonding and hydrophobic interactions, together with displaced water molecules. The data reported here represent a first step toward structure-based design of specific allosamidin derivatives. 相似文献
144.
van Spronsen PC Tak T Rood AM van Brussel AA Kijne JW Boot KJ 《Molecular plant-microbe interactions : MPMI》2003,16(1):83-91
LCOs (lipochitin oligosaccharides, Nod factors) produced by the rhizobial symbiote of Vicia sativa subsp. nigra (vetch, an indeterminate-type nodulating plant) are mitogenic when carrying an 18:4 acyl chain but not when carrying an 18:1 acyl chain. This suggests that the 18:4 acyl chain specifically contributes to signaling in indeterminate-type nodulation. In a working hypothesis, we speculated that the 18:4 acyl chain is involved in oxylipin signaling comparable to, for example, signaling by derivatives of the 18:3 fatty acid linolenic acid (the octadecanoid pathway). Because salicylic acid (SA) is known to interfere with oxylipin signaling, we tested whether nodulation of vetch could be affected by addition of 10(-4) M SA. This concentration completely blocked nodulation of vetch by Rhizobium leguminosarum bv. viciae and inhibited the mitogenic effect of 18:4 LCOs but did not affect LCO-induced root-hair deformation. SA did not act systemically, and only biologically active SA derivatives were capable of inhibiting nodule formation. SA also inhibited R. leguminosarum bv. viciae association with vetch roots. In contrast, addition of SA to Lotus japonicus (a determinate-type nodulating plant responding to 18:1 LCOs) did not inhibit nodulation by Mesorhizobium loti. Other indeterminate-type nodulating plants showed the same inhibiting response toward SA, whereas SA did not inhibit the nodulation of other determinate-type nodulating plants. SA may be a useful tool for studying fundamental differences between signal transduction pathways of indeterminate- and determinate-type nodulating plants. 相似文献
145.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献
146.
Boot J Cases M Clark BP Findlay J Gallagher PT Hayhurst L Man T Montalbetti C Rathmell RE Rudyk H Walter MW Whatton M Wood V 《Bioorganic & medicinal chemistry letters》2005,15(3):699-703
Novel arylthiomethyl morpholines are potent selective norepinephrine reuptake inhibitors (NERIs) and dual serotonin/norepinephrine reuptake inhibitors (SRI/NERIs). The target compounds were prepared using a stereochemically versatile synthesis featuring an aldol condensation as the key step. One enantiomer of the 2-methoxy-substituted analogue was found to be a potent and selective norepinephrine reuptake inhibitor, whereas the opposite enantiomer was a potent dual serotonin/norepinephrine reuptake inhibitor. 相似文献
147.
Claudia?Dumrese Christine?F?Maurus Daniel?Gygi M?rten?KJ?Schneider Michael?Walch Peter?Groscurth Urs?ZieglerEmail author 《BMC microbiology》2005,5(1):2
Background
The intracellular bacterium Chlamydia pneumoniae is suspected to play a role in formation and progression of atherosclerosis. Many studies investigated cell death initiation versus inhibition by Chlamydia pneumoniae in established cell lines but nothing is known in primary human aortic smooth muscle cells, a cell type among others known to be involved in the formation of the atherosclerotic plaque. Type of cell death was analyzed by various methods in primary aortic smooth muscle cells after infection with Chlamydia pneumoniae to investigate a possible pathogenic link in atherosclerosis. 相似文献148.
Fusetti F von Moeller H Houston D Rozeboom HJ Dijkstra BW Boot RG Aerts JM van Aalten DM 《The Journal of biological chemistry》2002,277(28):25537-25544
Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors. 相似文献
149.
150.