Chemistry:DOTAM
DOTAM (also sometimes known as TCMC) is an organic ligand used as a chelator much like its carboxylic acid analog DOTA, but shows greater selectivity for large covalently binding metal ions. It was designed and first synthesized by Robert D. Hancock and coworkers in 1995[1] for the selective complexation of the large covalently binding metal ions Cd(II) and Pb(II) based on Hancock’s theories of ligand design involving neutral oxygen donor atoms.[2] The name DOTAM derives from its carboxylic acid analog DOTA by addition of an M to designate through the AM ending the presence of amide rather than carboxylate groups,[1] as applies also to other ligands studied since such as EDTAM derived from EDTA. A derivative with a reactive linking group of para-isothiocyanatobenzyl attached to the cyclen ring for attachment to antibodies selective for particular types of cancer and in other applications is also of interest as a bifunctional chelator (BFC).[3][4]
At present the Pb-DOTAMTATE 212-Pb (alpha particle emitter) bioconjugate has been approved for clinical use in treating patients with gastroenteropancreatic neuroendocrine tumors (AlphaMedix press release).
References
- ↑ 1.0 1.1 Maumela, Hulsani; Hancock, Robert D.; Carlton, Lawrence; Reibensepies, Joseph H.; Wainwright, Kevin P. (1995). "The Amide Oxygen as a Donor Group. Metal Complexing Properties of tetra-N-acetamide substituted Cyclen - A Crystallographic, NMR, Molecular Mechanics, and Thermodynamic Study". J. Am. Chem. Soc. 117 (25): 6698-6707. https://pubs.acs.org/doi/10.1021/ja00130a008.
- ↑ Hancock, Robert D.; Martell, Arthur Earl (1989). "Ligand Design for Selective Complexation of Metal Ions in Aqueous Solution". Chemical Reviews 89 (8): 1875-1914. https://pubs.acs.org/doi/10.1021/cr00098a011.
- ↑ Stenberg, Vilde Yuli; Larsen, Roy Hartvig; Ma, Li-Wei; Peng, Qian; Juzenas, Petras; Bruland, Øyvind Sverre; Juzeniene, Asta (January 2021). "Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer". International Journal of Molecular Sciences 22 (9): 4815. https://pmc.ncbi.nlm.nih.gov/articles/PMC8124365/.
- ↑ Brennecke, Benjamin; Wang, Qinghua; Haap, Wolfgang; Grether, Uwe; Hu, Hai-Yu; Nazaré, Mark (2021-04-21). "DOTAM-Based, Targeted, Activatable Fluorescent Probes for the Highly Sensitive and Selective Detection of Cancer Cells". Bioconjugate Chemistry 32 (4): 702-712. https://pubs.acs.org/doi/10.1021/acs.bioconjchem.0c00699.
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