Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes
A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties to the receptor protein in comparison to the drug AMD3100 (Plerixafor, Mozobil). The interaction of the metallodrug has been optimized by using ultrarigid chelator units that...
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| Veröffentlicht in: | Journal of the American Chemical Society 2009-03, Vol.131 (10), p.3416-3417 |
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| container_end_page | 3417 |
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| container_issue | 10 |
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| container_title | Journal of the American Chemical Society |
| container_volume | 131 |
| creator | Khan, Abid Nicholson, Gary Greenman, John Madden, Leigh McRobbie, Graeme Pannecouque, Christophe De Clercq, Erik Ullom, Robert Maples, Danny L Maples, Randall D Silversides, Jon D Hubin, Timothy J Archibald, Stephen J |
| description | A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties to the receptor protein in comparison to the drug AMD3100 (Plerixafor, Mozobil). The interaction of the metallodrug has been optimized by using ultrarigid chelator units that offer an equatorial site for coordination to the amino acid side chains of the protein. Binding competition assays with anti-CXCR4 antibodies show that the new compound stays bound longer and it has improved anti-HIV potency in vitro (EC50 = 4.3 nM). X-ray structural studies using acetate as a model for carboxylate amino acid side chains indicate the nature of the coordination interaction. |
| doi_str_mv | 10.1021/ja807921k |
| format | Article |
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| identifier | ISSN: 0002-7863 |
| ispartof | Journal of the American Chemical Society, 2009-03, Vol.131 (10), p.3416-3417 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Anti-HIV Agents - pharmacology Metals - chemistry Models, Molecular Protein Binding Receptors, CXCR4 - antagonists & inhibitors Receptors, CXCR4 - chemistry Receptors, CXCR4 - metabolism |
| title | Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes |
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