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2.
Geoffrey R. Banks David G. Barker 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1985,826(4):180-185
Yeast DNA ligase is radioactively labelled in vitro by incubating a crude cell extract with [α-32P]ATP. The product of this reaction is the stable covalent ligase-AMP adduct, which can be characterized by its reactivity with either pyrophosphate or nicked DNA and visualized by gel electrophoresis and autoradiography. The Saccharomyces cerevisiae DNA ligase was identified as an 89 kDa polypeptide by exploiting the fact that transformants with multiple copies of the plasmid-encoded DNA ligase (CDC9) gene overproduce the enzyme by two orders of magnitude. A similar strategy has been used to identify the Schizosaccharomyces pombe DNA ligase as an 87 kDa polypeptide. Both values agree well with the coding capacities of the respective cloned gene sequences. When the S. cerevisiae ligase is greatly overproduced with respect to wild-type levels, a second polypeptide of 78.5 kDa is also labelled and has the same properties as the 89 kDa adduct. We suggest that this polypeptide is generated by proteolysis. 相似文献
3.
The l-thyroxine binding site in human serum thyroxine-binding globulin was investigated by affinity labeling with N-bromoacetyl-l-thyroxine (BrAcT4). Competitive binding studies showed that, in the presence of 100 molar excess of BrAcT4, binding of thyroxine to thyroxine-binding globulin was nearly totally abolished. The reaction of BrAcT4 to form covalent binding was inhibited in the presence of thyroxine and the affinity-labeled thyroxinebinding globulin lost its ability to bind thyroxine. These results indicate BrAcT4 and thyroxine competed for the same binding site. Affinity labeling with 2 mol of BrAcT4/mol of thyroxine-binding globulin resulted in the covalent attachment of 0.7 mol of ligand. By amino acid analysis and high voltage paper electrophoresis, methionine was identified as the major residue labeled (75%). Lysine, tyrosine, and histidine were also found to be labeled to the extent of 8, 8, and 5%, respectively. 相似文献
4.
Paul D. Bonnitcha Simon R. Bayly Mark B.M. Theobald Helen M. Betts Jason S. Lewis Jonathan R. Dilworth 《Journal of inorganic biochemistry》2010,104(2):126-9888
Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. 64Cu-ATSM) and nitroimidazoles (e.g. 18F-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H2ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H2ATSM/en. Oxygen-dependent uptake studies were performed using the 64Cu radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted 64Cu-ATSM/A derivatives. The 2-nitroimidazole derivative of 64Cu-ATSM/en demonstrated superior hypoxia selectivity to 64Cu-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A. 相似文献
5.
Temperature affects both the biology and morphology of mosquito vectors. Geometric morphometrics is a useful new tool for capturing and analyzing differences in shape and size in many morphological parameters, including wings. We have used this technique for capturing the differences in the wings of the malaria vector Anopheles superpictus, using cohorts reared at six different constant temperatures (15°, 20°, 25°, 27°, 30°, and 35° C) and also searched for potential correlations with the life tables of the species. We studied wing shape in both male and female adults, using 22 landmarks on the wing in relation to ecological parameters, including the development rate. The ecological zero was calculated as 9.93° C and the thermal constant as 296.34 day‐degrees. The rearing temperature affects egg, larval, and pupal development and also the total time from egg to adult. As rearing temperatures increased, longevity decreased in both sexes. In An. superpictus, Ro value and productivity correlated with the statistically significant gradual deformations in the wing shape related to size in both sexes. These deformations directly linked to differences in immature rearing temperatures. Analysis using PCA and UPGMA phenograms showed that although wings of females became narrower dorsoventrally as the temperature increased, they became broader in males. Comparisons of the wing landmarks indicated the medial part of the wing was most affected by larval rearing temperatures, showing relatively more deformations. Algorithmic values of the life tables were determined in correlation with the results of geometric morphometrics. Comparisons of centroid sizes in the cohorts showed that overall wing size became smaller in both sexes in response to higher rearing temperatures. 相似文献
6.
《Bioorganic & medicinal chemistry》2016,24(18):4444-4451
Nowadays, AT1 receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1 receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1 receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199 nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities. 相似文献
7.
Focal contacts of spreading platelets with the substratum 总被引:1,自引:0,他引:1
Contacts with glass substratum formed by the spreading rabbit platelets were examined by an antibody-exclusion method; monoclonal antibodies against 80 kD bovine serum protein were used. It was found that platelets form focal contacts in the course of spreading. The size of the largest focal contacts formed by platelets is smaller than that of the contacts formed by fibroblasts. The antibody-exclusion method revealed focal contacts of platelets much more clearly than interference reflection microscopy (IRM). The similarity of reactions involved in spreading platelets and of large nucleus-containing tissue cells is discussed. 相似文献
8.
9.
T. Phanitchat C. Apiwathnasorn S. Sungvornyothin Y. Samung S. Dujardin J.‐P. Dujardin S. Sumruayphol 《Medical and veterinary entomology》2019,33(4):476-484
Wing geometry helps to identify mosquito species, even cryptic ones. On the other hand, temperature has a well‐known effect on insect metric properties. Can such effects blur the taxonomic signal embedded in the wing? Two strains of Aedes albopictus (laboratory and field strain) were examined under three different rearing temperatures (26, 30 and 33 °C) using landmark‐ and outline‐based morphometric approaches. The wings of each experimental line were compared with Aedes aegypti. Both approaches indicated similar associations between wing size and temperature. For the laboratory strain, the wing size significantly decreased as the temperature increased. For the field strain, the largest wings were observed at the intermediate temperature. The two morphometric approaches describing shape showed different sensibilities to temperature. For both strains and sexes, the landmark‐based approach disclosed significant wing shape changes with temperature changes. The outline‐based approach showed lesser effects, detecting significant changes only in laboratory females and in field males. Despite the size and shape changes induced by temperature, the two strains of Ae. albopictus were always distinguished from Ae. aegypti. The present study confirms the lability of size. However, it also suggests that, despite environmentally‐induced variation, the architecture of the wing still provides a strong taxonomic signal. 相似文献
10.
Monica BreurkenEdith H.M. Lempens Rinske P. TemmingBrett A. Helms E.W. MeijerMaarten Merkx 《Bioorganic & medicinal chemistry》2011,19(3):1062-1071
Collagen is an attractive marker for tissue remodeling in a variety of common disease processes. Here we report the preparation of protein dendrimers as multivalent collagen targeting ligands by native chemical ligation of the collagen binding protein CNA35 to cysteine-functionalized dendritic divalent (AB2) and tetravalent (AB4) wedges. The binding of these multivalent protein constructs was studied on collagen-immobilized chip surfaces as well as to native collagen in rat intestinal tissues. To understand the importance of target density we also created collagen-mimicking surfaces by immobilizing synthetic collagen triple helical peptides at various densities on a chip surface. Multivalent display of a weak-binding variant (CNA35-Y175K) resulted in a large increase in collagen affinity, effectively restoring the collagen imaging capacities for the AB4 system. In addition, dissociation of these multivalent CNA35 dendrimers from collagen surfaces was found to be strongly attenuated. 相似文献