For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.
The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dibydro-5,6-debydrokawain was isolated by a simple method without chromatography from the leaves of A/pima speciosa K. SCHUM. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents.Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl]phosphorothionate (4) had the strongest antifungal activity of 91 % at 100 ppm against Corticium rolfsii.
The three-dimensional structure of omega-amino acid:pyruvate aminotransferase from Pseudomonas sp. F-126, an isologous alpha 4 tetramer containing pyridoxal 5'-phosphate (PLP) as a cofactor, has been determined at 2.0 A resolution. The diffraction data were collected with a newly developed Weissenberg camera with a Fuji Imaging Plate, using synchrotron radiation. The mean figure-of-merit was 0.57. The subunit is rich in secondary structure and comprises two domains. PLP is located in the large domain. The high homology in the secondary structure between this enzyme and aspartate aminotransferase strongly indicates that these two types of enzymes have evolved from a common ancestor.
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