Bifunctional chelates

Monoamine Oxidases and their Inhibitors. Figure 2 Structures of MAO inhibitors. In the top row, the structural similarity between selegiline/L-deprenyl and methamphetamine is shown. Below are the aminoindan series of propargylamine compounds such as rasagiline. Next, the bifunctional MAO and cholinesterase inhibitors (ladostigil) and lastly, the iron chelator-MAO inhibitors. 

The binding sites of platinum to DNA and its separate bases are expected to be similar to those for the other -metals, provided that the platinum binds through one site only. However both PtClf- and such molecules as Pt(NH3)2Cl2, cis- and trans-iorms, can act bifunctionally. Indeed preferential binding is expected to yield chelated complexes of one type or another. For example the cis-chelation will lead to the following complexes. 

Develop bifunctional ligands which NCI, NIH have a high affinity for Pb(ll) and Bi(lll) systematic exploration of incorporating thiol donor groups into chelating agents... 

Fig. IS. DTS derivatives as used in the bifunctional chelating approach to label proteins with technetium...

Fig. 8. Example of "mTcO-DADT bifunctional chelating agents R = sidechain for attachment to biomolecule...

E. Benoist, A. Loussouam, P. Remaud, J. C. Chatal, and J. F. Gestin, Convenient and simplified approaches to V-monoprotected triaminopropane derivatives. Key intermediates for bifunctional chelating agent synthesis, Synthesis (1998) 1113-1118. 

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. 

Other chelate-dendrimer constructs may be prepared using alternative bifunctional chelating agents according to Chapter 10. 

Determine the amount of adsorbed protein on the particles by using a suitable protein assay technique, such as the bifunctional chelating agents (BCA) Protein Assay (Thermo Fisher). 

Figure 20.18 The bifunctional chelating reagent DTPA may be used to modify amine groups on antibody molecules, forming amide bond linkages. Indium-111 then may be complexed to the chelator group to create a radiolabeled-targeting reagent.

Certain bifunctional metal chelating agents have been used to investigate protein interactions by virtue of their ability to generate reactive oxygen species that affects protein structure in the immediate vicinity of their modification site. The following sections discuss two applications of such chelate labels, one of which cleaves peptide bonds while the other one causes covalent crosslinks to occur between interacting protein structures. 

Figure 28.17 FeBABE is a bifunctional chelating agent containing an EDTA group on one side and a thiol-reactive bromoacetyl group on the other end. The EDTA group is coordinated with an iron ion.

Brechbiel, M.W., McMurry, T.J., and Gansow, O.A. (1993) A direct synthesis of a bifunctional chelating agent for radiolabeling proteins. Tetrahedron Lett. 34, 3691-3694. 

Moi, M.K., Meares, C.F., McCall, M.J., Cole, W.C., and DeNardo, S.J. (1985) Copper chelates as probes of biological systems stable copper complexes with a macrocyclic bifunctional chelating agent. Anal. Biochem. 148, 249-253. 

Pandurangi, R.S. et al. (1997b) Chemistry of bifunctional photoprobes Part 1. Perfluoro azido functionalized phosphorus hydrazides as novel photoreactive heterobifunctional chelating agents High efficiency nitrene insertion on model solvents and proteins./. Org. Chem. 62(9), 2798-2807. 

Renn, O., and Meares, C.F. (1992) Large scale synthesis of the bifunctional chelating agent 2-p-nitroben-zyl-l,4,7,10-tetraazacyclododecane-N,N, N"N" -tetraacetic acid and the determination of its enantiomeric purity by chiral chromatography. Bioconjugate Chem. 3, 563-569. 

Subramanian, R., and Meares, C.F. (1991) Bifunctional chelating agents for radiometal-labeled monoclonal antibodies. In Cancer Imaging with Radiolabeled Antibodies (D.M. Coldenberg, ed.), pp. 183-199. Kluwer, Boston, MA. 

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