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111.
The RING finger domain of the Mdm2, located at the C‐terminus of the protein, is necessary for regulation of p53, a tumor suppressor protein. The 48‐residues long Mdm2 peptide is an important target for studying its interaction with small anticancer drug candidates. For the chemical synthesis of the Mdm2 RING finger domain, the fragment condensation on solid‐phase and the fragment condensation in solution were studied. The latter method was performed using either protected or free peptides at the C‐terminus as the amino component. Best results were achieved using solution condensation where the N‐component was applied with the C‐terminal carboxyl group left unprotected. The developed method is well suited for large‐scale synthesis of Mdm2 RING finger domain, combining the advantages of both solid‐phase and solution synthesis. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
112.
Evaluation of tubulointerstitial lesions' severity in patients with glomerulonephritides: an NMR-based metabonomic study 总被引:1,自引:0,他引:1
Psihogios NG Kalaitzidis RG Dimou S Seferiadis KI Siamopoulos KC Bairaktari ET 《Journal of proteome research》2007,6(9):3760-3770
An 1H NMR-based metabonomic approach was used to investigate the correlation of histopathologically assessed tubulointerstitial lesions with the urinary metabolite profile in 77 patients with glomerulonephritides submitted to renal biopsy. The presence of renal damage was predicted with a sensitivity of 96% and a specificity of 99%. Patients with mild, moderate, and severe tubulointerstitial lesions were progressively differentiated from the healthy individuals in the Orthogonal Signal Correction Partial Least-Squares-Discriminant Analysis (OSC/PLS-DA) models with a statistically significant separation between those with mild and with severe lesions. The onset of the tubulointerstitial lesions is characterized by decreased excretion of citrate, hippurate, glycine, and creatinine, whereas further deterioration is followed by glycosuria, selective aminoaciduria, total depletion of citrate and hippurate, and gradual increase in the excretion of lactate, acetate, and trimethylamine-N-oxide. NMR-based metabonomic urinalysis could contribute to the early evaluation of the severity of the renal damage and possibly to the monitoring of kidney function. 相似文献
113.
We present the characterization of BmVMP90, a vitelline membrane protein (VMP) of the silkmoth Bombyx mori bearing similarities with dipteran VMPs whose existence had recently been suggested by an in silico analysis of the silkmoth genome and follicular cell RNA expression analyses. Using a specific antibody, we determine the presence of BmVMP90 protein in ovarian follicular cell extracts at the end of vitellogenesis and in vitelline membrane extracts but not in the chorion of fractionated eggshells isolated from ovulated follicles. Whole mount follicle immunofluorescence studies reveal a pattern of BmVMP90 deposition matching the ?imprinted? pattern of follicular cells on the vitelline membrane surface. Antisense DNA-directed inhibition BmVMP90 expression in ex?vivo cultures of early vitellogenic follicles produced a phenotype of kidney- or bean-shaped follicles with detached follicular epithelia, suggestive of the importance of BmVMP90 for the integrity of developing follicles and normal deposition of the chorion structure that follows vitelline membrane formation but no adverse effects on the execution of the follicular cell-imprinted program of choriogenesis per se. 相似文献
114.
Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression 总被引:14,自引:0,他引:14
115.
Functionalized carbon nanotubes (f-CNT) are emerging as a new family of nanovectors for the delivery of different types of therapeutic molecules. The application of CNT in the field of carrier-mediated delivery has become possible after the recent discovery of their capacity to penetrate into the cells. CNT can be loaded with active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Once the cargos are carried into various cells, tissues and organs they are able to express their biological function. In this review, we will describe the potential of f-CNT to deliver different types of therapeutic molecules. 相似文献
116.
Schofield G Bishop CM Katselidis KA Dimopoulos P Pantis JD Hays GC 《The Journal of animal ecology》2009,78(1):14-21
1. Reproductive fitness is often compromised at the margins of a species' range due to sub-optimal conditions. 2. Set against this backdrop, the Mediterranean's largest loggerhead sea turtle (Caretta caretta) rookery at Zakynthos (Greece) presents a conundrum, being at a very high latitude for this species, yet hosting a high concentration of nesting. 3. We used visual surveys combined with global positioning system (GPS) tracking to show that at the start of the breeding season, individuals showed microhabitat selection, with females residing in transient patches of warm water. As the sea warmed in the summer, this selection was no longer evident. 4. As loggerhead turtles are ectothermic, this early season warm-water selection presumably speeds up egg maturation rates before oviposition, thereby allowing more clutches to be incubated when sand conditions are optimal during the summer. 5. Active selection of warm waters may allow turtles to initiate nesting at an earlier date. 相似文献
117.
118.
Most of the mitochondrial inner-membrane proteins are generated without a presequence and their targeting depends on inadequately defined internal segments. Despite the numerous components of the import machinery identified by proteomics, the properties of hydrophobic import substrates remain poorly understood. Recent studies support several principles for these membrane proteins: first, they become organized into partially assembled forms within the translocon; second, they present noncontiguous targeting signals; and third, they induce conformational changes in translocase subunits, thereby mediating "assembly on demand" of the import machinery. It is possible that the energy needed for these proteins to pass across the outer membrane, to travel through the intermembrane space and to target the inner-membrane surface is provided by conformational changes involving import components that seem to have natively unfolded structures. Such structural malleability might render some of the translocase subunits more adept at driving the protein import process. 相似文献
119.
Areti Kokkinou Michael Karpusas Kostas Bethanis Dimitris Mentzafos 《Carbohydrate research》2010,345(8):1034-1040
The inclusion of (R)- and (S)-camphor compounds in α-cyclodextrin has been studied by X-ray crystallography. The crystal structures of the complexes reveal that one guest molecule is accommodated inside the cavity formed by a head-to-head cyclodextrin dimer. In the crystal lattice, the dimers form layers which are successively shifted by half a dimer. In both (R)- and (S)-cases, the camphor molecule exhibits disorder and occupies three major sites with orientations that can be described as either ‘polar’ or ‘equatorial’. Molecular dynamics simulations performed for the observed complexes indicate that although the carbonyl oxygen of both (R)- and (S)-camphor switches between different hydrogen bonding partners, it maintains the observed mode of ‘polar’ or ‘equatorial’ alignment. 相似文献
120.
Alexacou KM Tenchiu Deleanu AC Chrysina ED Charavgi MD Kostas ID Zographos SE Oikonomakos NG Leonidas DD 《Bioorganic & medicinal chemistry》2010,18(22):7911-7922
Glycogen phosphorylase (GP) is a promising target for the treatment of type 2 diabetes. In the process of structure based drug design for GP, a group of 15 aromatic aldehyde 4-(β-d-glucopyranosyl)thiosemicarbazones have been synthesized and evaluated as inhibitors of rabbit muscle glycogen phosphorylase b (GPb) by kinetic studies. These compounds are competitive inhibitors of GPb with respect to α-d-glucose-1-phosphate with IC50 values ranging from 5.7 to 524.3 μM. In order to elucidate the structural basis of their inhibition, the crystal structures of these compounds in complex with GPb at 1.95–2.23 Å resolution were determined. The complex structures reveal that the inhibitors are accommodated at the catalytic site with the glucopyranosyl moiety at approximately the same position as α-d-glucose and stabilize the T conformation of the 280s loop. The thiosemicarbazone part of the studied glucosyl thiosemicarbazones possess a moiety derived from substituted benzaldehydes with NO2, F, Cl, Br, OH, OMe, CF3, or Me at the ortho-, meta- or para-position of the aromatic ring as well as a moiety derived from 4-pyridinecarboxaldehyde. These fit tightly into the β-pocket, a side channel from the catalytic site with no access to the bulk solvent. The differences in their inhibitory potency can be interpreted in terms of variations in the interactions of the aldehyde-derived moiety with protein residues in the β-pocket. In addition, 14 out of the 15 studied inhibitors were found bound at the new allosteric site of the enzyme. 相似文献