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Ng PS Pingle MR Balasundarum G Friedman A Zu X Bergstrom DE 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1635-1637
The syntheses of endcaps for covalently linking the 3' and 5' hydroxyl groups of blunt end double-stranded DNA are described. Endcap diols were converted into DMTr protected phosphoramidites and incorporated between nucleotides 4 and 5 of a self-complementary octamer. The stabilizing effect of the endcaps on duplex DNA was determined by Tm experiments on the self-complementary octamer. 相似文献
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Targeting to rhoptry organelles of Toxoplasma gondii involves evolutionarily conserved mechanisms 总被引:1,自引:0,他引:1
Intracellular parasites of the phylum Apicomplexa contain specialized rhoptry secretory organelles that have a crucial function in host-cell invasion and establishment of the parasitophorous vacuole. Here we show that localization of the Toxoplasma gondii rhoptry protein ROP2 is dependent on a YEQL sequence in the cytoplasmic tail that binds to micro-chain subunits of T. gondii and mammalian adaptors, and conforms to the YXXstraight phi mammalian sorting motif. Chimaeric reporters, containing the transmembrane domains and cytoplasmic tails of the low-density lipoprotein receptor and of Lamp-1, are sorted to the Golgi or the trans-Golgi network (TGN), and partially to apical microneme organelles of the parasite, respectively. Targeting of these reporters is mediated by YXXstraight phi- and NPXY-type signals. This is the first demonstration of tyrosine-dependent sorting in protozoan parasites, indicating that T. gondii proteins may be targeted to, and involved in biogenesis of, morphologically unique organelles through the use of evolutionarily conserved signals and machinery. 相似文献
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Long duration mild hyperthermia (LDMH) has been shown to be an effective radiosensitizer when combined with low dose rate irradiation and pulsed low dose rate irradiation. These protocols are being investigated to determine if these effects can be related to DNA double strand breakage (dsb). In our studies we used human melanoma (SK mel-3) and fibroblasts (AG1522). A low dose rate was given at 0.88 cGy/min while pulsed doses were given at 150 cGy/min. Our results showed that the degree of thermal radiosensitization (TER) increased as the average dose rate decreased. This was seen for both the survival endpoints and the degree of DNA strand breaks. There was a very good correlation between the TER and the degree of DNA strand breaks.In conclusion our data show that LDMH is an effective radiosensitizer for both LDR and PSLDR and this may also be an effective clinical protocol. The quantity of DNA dsb's appears to be related to TER and may be predictive of the degree of radiosensitization. 相似文献
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PseudoBase is a database containing structural, functional and sequence data related to RNA pseudo-knots. It can be reached at http://wwwbio.Leiden Univ.nl/ approximately Batenburg/PKB.html. This page will direct the user to a retrieval page from where a particular pseudoknot can be chosen, or to a submission page which enables the user to add pseudoknot information to the database or to an informative page that elaborates on the various aspects of the database. For each pseudoknot, 12 items are stored, e.g. the nucleotides of the region that contains the pseudoknot, the stem positions of the pseudoknot, the EMBL accession number of the sequence that contains this pseudoknot and the support that can be given regarding the reliability of the pseudoknot. Access is via a small number of steps, using 16 different categories. The development process was done by applying the evolutionary methodology for software development rather than by applying the methodology of the classical waterfall model or the more modern spiral model. 相似文献
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Liang M Mallari C Rosser M Ng HP May K Monahan S Bauman JG Islam I Ghannam A Buckman B Shaw K Wei GP Xu W Zhao Z Ho E Shen J Oanh H Subramanyam B Vergona R Taub D Dunning L Harvey S Snider RM Hesselgesser J Morrissey MM Perez HD 《The Journal of biological chemistry》2000,275(25):19000-19008
The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. Through high capacity screening followed by chemical optimization, we identified a novel non-peptide CCR1 antagonist, R-N-[5-chloro-2-[2-[4-[(4-fluorophenyl)methyl]-2-methyl-1-piperazinyl ]-2-oxoethoxy]phenyl]urea hydrochloric acid salt (BX 471). Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3) with high affinity (K(i) ranged from 1 nm to 5.5 nm). BX 471 was a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX 471 demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. Pharmacokinetic studies demonstrated that BX 471 was orally active with a bioavailability of 60% in dogs. Furthermore, BX 471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. This study is the first to demonstrate that a non-peptide chemokine receptor antagonist is efficacious in an animal model of an autoimmune disease. In summary, we have identified a potent, selective, and orally available CCR1 antagonist that may be useful in the treatment of chronic inflammatory diseases. 相似文献