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901.
902.
Jens-Uwe Peters Holger Kühne Henrietta Dehmlow Uwe Grether Aurelia Conte Dominik Hainzl Cornelia Hertel Nicole A. Kratochwil Michael Otteneder Robert Narquizian Constantinos G. Panousis Fabienne Ricklin Stephan Röver 《Bioorganic & medicinal chemistry letters》2010,20(18):5426-5430
Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization. 相似文献
903.
Ravn P Stahn R Danielczyk A Faulstich D Karsten U Goletz S 《Cancer immunology, immunotherapy : CII》2007,56(9):1345-1357
The Thomsen-Friedenreich disaccharide (TFα) is a promising antigen for tumor immunotargeting, since it is almost exclusively expressed on carcinoma tissues. So far,
an obstacle preventing the exploitation of TF for immunotargeting has been the lack of suitable (non-IgM) antibodies with
high affinity and specificity. Recently we reported on a novel strategy for generating antibodies toward small uncharged carbohydrates
and the generation of recombinant antibodies toward TF. Among them, two multivalent scFv antibodies showed sub-micromolar
functional affinities and appeared well suited for immunotargeting. In the present study, the trimeric scFv(1aa) and the tetrameric
scFv(0aa) have been further developed for radioimmunotargeting. The scFvs were radiolabeled with 111In using DTPA as chelator without losing binding activity or molecular stoichiometry. Binding affinities as high as 1 × 10−7 M toward TF displayed on living cells were determined. Antibody biodistribution and tumor targeting efficacy were studied
in TF-positive human breast cancer (ZR-75-1) bearing mice. TF was successfully targeted in vivo with tumor uptakes of ∼11
and 8% ID/g after 24 h for the trimeric and tetrameric scFv, respectively. These results validate TF as a potent antigen for
tumor targeting. The biodistribution of the scFvs was comparable to that reported for IgGs. In contrast to the IgGs, the serum
clearance of the scFvs was very fast, which could be an advantage in a therapeutic setting. Furthermore, kidney uptake, which
is often critical for small recombinant antibodies labeled with radio-metals, was low with the tetramer (11% ID/g). We conclude
that the multimeric anti-TF scFvs are promising candidates to be further developed toward therapeutic application.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
904.
Nature of the periplastidial pathway of starch synthesis in the cryptophyte Guillardia theta 下载免费PDF全文
Deschamps P Haferkamp I Dauvillée D Haebel S Steup M Buléon A Putaux JL Colleoni C d'Hulst C Plancke C Gould S Maier U Neuhaus HE Ball S 《Eukaryotic cell》2006,5(6):954-963
The nature of the periplastidial pathway of starch biosynthesis was investigated with the model cryptophyte Guillardia theta. The storage polysaccharide granules were shown to be composed of both amylose and amylopectin fractions with a chain length distribution and crystalline organization very similar to those of starch from green algae and land plants. Most starch granules displayed a shape consistent with biosynthesis occurring around the pyrenoid through the rhodoplast membranes. A protein with significant similarity to the amylose-synthesizing granule-bound starch synthase 1 from green plants was found as the major polypeptide bound to the polysaccharide matrix. N-terminal sequencing of the mature protein proved that the precursor protein carries a nonfunctional transit peptide in its bipartite topogenic signal sequence which is cleaved without yielding transport of the enzyme across the two inner plastid membranes. The enzyme was shown to display similar affinities for ADP and UDP-glucose, while the V(max) measured with UDP-glucose was twofold higher. The granule-bound starch synthase from Guillardia theta was demonstrated to be responsible for the synthesis of long glucan chains and therefore to be the functional equivalent of the amylose-synthesizing enzyme of green plants. Preliminary characterization of the starch pathway suggests that Guillardia theta utilizes a UDP-glucose-based pathway to synthesize starch. 相似文献
905.
Uwe Parsch Karlheinz Wörner Joachim W. Engels 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1641-1643
Abstract Here we present a method based on CD spectroscopy to evaluate duplex and triplex melting independent from each other in cases where UV melting curves show only one transition. 相似文献
906.
Frequent gene movement and pseudogene evolution is common to the large and complex genomes of wheat, barley, and their relatives 总被引:1,自引:0,他引:1
Wicker T Mayer KF Gundlach H Martis M Steuernagel B Scholz U Simková H Kubaláková M Choulet F Taudien S Platzer M Feuillet C Fahima T Budak H Dolezel J Keller B Stein N 《The Plant cell》2011,23(5):1706-1718
All six arms of the group 1 chromosomes of hexaploid wheat (Triticum aestivum) were sequenced with Roche/454 to 1.3- to 2.2-fold coverage and compared with similar data sets from the homoeologous chromosome 1H of barley (Hordeum vulgare). Six to ten thousand gene sequences were sampled per chromosome. These were classified into genes that have their closest homologs in the Triticeae group 1 syntenic region in Brachypodium, rice (Oryza sativa), and/or sorghum (Sorghum bicolor) and genes that have their homologs elsewhere in these model grass genomes. Although the number of syntenic genes was similar between the homologous groups, the amount of nonsyntenic genes was found to be extremely diverse between wheat and barley and even between wheat subgenomes. Besides a small core group of genes that are nonsyntenic in other grasses but conserved among Triticeae, we found thousands of genic sequences that are specific to chromosomes of one single species or subgenome. By examining in detail 50 genes from chromosome 1H for which BAC sequences were available, we found that many represent pseudogenes that resulted from transposable element activity and double-strand break repair. Thus, Triticeae seem to accumulate nonsyntenic genes frequently. Since many of them are likely to be pseudogenes, total gene numbers in Triticeae are prone to pronounced overestimates. 相似文献
907.
Fossen T Wray V Bruns K Rachmat J Henklein P Tessmer U Maczurek A Klinger P Schubert U 《The Journal of biological chemistry》2005,280(52):42515-42527
The human immunodeficiency virus type 1 p6 protein represents a docking site for several cellular and viral binding factors and fulfills major roles in the formation of infectious viruses. To date, however, the structure of this 52-amino acid protein, by far the smallest lentiviral protein known, either in its mature form as free p6 or as the C-terminal part of the Pr55 Gag polyprotein has not been unraveled. We have explored the high resolution structure and folding of p6 by CD and NMR spectroscopy. Under membranous solution conditions, p6 can adopt a helix-flexible helix structure; a short helix-1 (amino acids 14-18) is connected to a pronounced helix-2 (amino acids 33-44) by a flexible hinge region. Thus, p6 can be subdivided into two distinct structural and functional domains; helix-2 perfectly defines the region that binds to the virus budding factor AIP-1/ALIX, indicating that this structure is required for interaction with the endosomal sorting complex required for transport. The PTAP motif at the N terminus, comprising the primary late assembly domain, which is crucial for interaction with another cellular budding factor, Tsg101, does not exhibit secondary structure. However, the adjacent helix-1 may play an indirect role in the specific complex formation between p6 and the binding groove in Tsg101. Moreover, binding studies by NMR demonstrate that helix-2, which also comprises the LXXLF motif required for incorporation of the human immunodeficiency virus type 1 accessory protein Vpr into budding virions, specifically interacts with the Vpr binding region, indicating that under the specific solution conditions used for structure analysis, p6 adopted a functional conformation. 相似文献
908.
Greiner S Wang X Herrmann RG Rauwolf U Mayer K Haberer G Meurer J 《Molecular biology and evolution》2008,25(9):2019-2030
A unique combination of genetic features and a rich stock of information make the flowering plant genus Oenothera an appealing model to explore the molecular basis of speciation processes including nucleus-organelle coevolution. From representative species, we have recently reported complete nucleotide sequences of the 5 basic and genetically distinguishable plastid chromosomes of subsection Oenothera (I-V). In nature, Oenothera plastid genomes are associated with 6 distinct, either homozygous or heterozygous, diploid nuclear genotypes of the 3 basic genomes A, B, or C. Artificially produced plastome-genome combinations that do not occur naturally often display interspecific plastome-genome incompatibility (PGI). In this study, we compare formal genetic data available from all 30 plastome-genome combinations with sequence differences between the plastomes to uncover potential determinants for interspecific PGI. Consistent with an active role in speciation, a remarkable number of genes have high Ka/Ks ratios. Different from the Solanacean cybrid model Atropa/tobacco, RNA editing seems not to be relevant for PGIs in Oenothera. However, predominantly sequence polymorphisms in intergenic segments are proposed as possible sources for PGI. A single locus, the bidirectional promoter region between psbB and clpP, is suggested to contribute to compartmental PGI in the interspecific AB hybrid containing plastome I (AB-I), consistent with its perturbed photosystem II activity. 相似文献
909.
A Bierhaus T Fleming S Stoyanov A Leffler A Babes C Neacsu SK Sauer M Eberhardt M Schnölzer F Lasischka WL Neuhuber TI Kichko I Konrade R Elvert W Mier V Pirags IK Lukic M Morcos T Dehmer N Rabbani PJ Thornalley D Edelstein C Nau J Forbes PM Humpert M Schwaninger D Ziegler DM Stern ME Cooper U Haberkorn M Brownlee PW Reeh PP Nawroth 《Nature medicine》2012,18(9):1445
910.
Spiwoks-Becker I Maus C tom Dieck S Fejtová A Engel L Wolloscheck T Wolfrum U Vollrath L Spessert R 《Cell and tissue research》2008,333(2):185-195
Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13-1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13-1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation. 相似文献