Chelates conjugation

Open-chain ligands were the first evaluated for complexation studies with indium and yttrium. The use of diethylenetriaminepentaacetic acid (DTPA) anhydride permitted early evaluation of labeled chelate-conjugates (Figure 2).80 The use of this activated chelating agent was quite popular, until the drawbacks associated with its crosslinking of proteins became apparent. 

Add a quantity of the SCN-Bzl-DTPA bifunctional chelating agent to obtain the desired molar excess of label over the amount of dendrimer present. The optimal ratio may be determined experimentally by preparing a series of dendrimer-chelate conjugates using different molar ratios and choosing the one that works the best in the intended application. 

It has been demonstrated that monoclonal antibodies may be chemically modified by reaction with metal chelates without loss of antibody activity or specificity. A radionuclide generator has been made to provide a source for Bi-212 to be used for attachment of bismuth chelates to antibody. Such antibody-metal-chelate conjugates appear to be stable in vivo and may provide a new method for radiotherapy. 

Electrochemiluminescence (ECL) is a homogeneous, bead-based technology using the Origen platform. ECL utilises ruthenium chelates conjugated to an... 

Kurihara A, Deguchi Y, Pardridge WM. Epidermal growth factor radiopharmaceuticals In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors. Bio-conjug Chem 1999 10 502-511. 

Watanabe N, Goodwin D A, Meares C F, et al. (1994). Immmunogenicity in rabbits and mice of an antibody-chelate conjugate Comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent. Cancer Res. 54 1049-1054. 

Glogard et have devised a novel contrast agent which is responsive to the concentration of free radicals. They used a Gd-chelate conjugated to a liposome by a disulfide linkage. Radical-induced cleavage of the disulfide bond frees the Gd-chelate from the liposome, reducing its relaxivity (due to faster reorientation). They report in vitro tests in which gamma radiation and dithiothreitol were both used to cleave the disulfide bond. 

Kukis. D.L. Diril, H. Greiner, D.P. De Nardo, G.L. Salako. Q.A. Meares. C.F. A comparative study of copper-67 radiolabeling and kinetic stabilities of antibody-macrocycle chelate conjugates. Cancer 1994, 73. 779. 

Percentage of radiometal-labeled biomolecule-chelator conjugate... 

The feasibility of designing polymer-chelator conjugates from which release of the chelator is triggered reversibly by the appearance of the target (toxic) metal in the circulatory system was tested by synthesis and measurement of the rates of metal-catalysis hydrolysis of the ester of poly(vinyl alcohol) and quinaldic acid at pH 7.5. Hydrolysis in 50% aqueous ethanol solution in the presence of the four m.etals, Cu(II), Ni(II), CodI) and Zn(II) at pH 7.5 was first order, with half lives of 67, 71, 172 and 476 min., respectively. The rate of hydrolysis in the absence of metals was not measurable. A double reciprocal plot of kobs vs. [M] for Ni(II) exhibited the expected linearity. For films of the ester, the deviation from first order kinetics was consistent with a contributing diffusion process. 

Spirodienone 28 arose through decarboxylation of the corresponding P-keto acid 27, which was obtained by proton loss from C9 and concomitant cleavage of the 1,10-bond — a process that would be favored in the chelated conjugated cyclopropyl intermediate 26b (Scheme 4). 

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