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American Chemical Society, Journal of the American Chemical Society, 10(131), p. 3416-3417, 2009

DOI: 10.1021/ja807921k

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Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes

Journal article published in 2009 by Abid Khan, Gary Nicholson, John Greenman, Leigh Madden, Graeme McRobbie, Christophe Pannecouque, Erik De Clercq, Robert Ullom, Danny L. Maples, Randall D. Maples, Jon D. Silversides, Timothy J. Hubin ORCID, Stephen J. Archibald
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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 (EC(50) = 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. ; Times Cited: 26