A Sulfur Tripod Glycoconjugate that Releases a High‐Affinity Copper Chelator in Hepatocytes

Pujol, Anaïs M.; Cuillel, Martine; Jullien, Anne-Solène; Lebrun, Colette; Cassio, Doris; Mintz, Elisabeth; Gateau, Christelle; Delangle, Pascale

doi:10.1002/anie.201203255

Cited by 49 publications

(58 citation statements)

References 28 publications

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“…Conversely, the chelation of copper with high affinity ligands might offer avenues for the treatment of diseases associated with copper overload such as Alzheimer’s and Wilson’s disease. 55 Most importantly, we anticipate that these reagents will facilitate the reliable measurement of Cu(I) binding affinities of metalloproteins and other biologically relevant Cu(I)ligands.…”

Section: Discussionmentioning

confidence: 99%

Robust Affinity Standards for Cu(I) Biochemistry

et al. 2013

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The measurement of reliable Cu(I) protein binding affinities requires competing reference ligands with similar binding strengths; however, the literature on such reference ligands is not only sparse but often conflicting. To address this deficiency, we have created and characterized a series of water-soluble monovalent copper ligands, MCL-1, MCL-2, and MCL-3, that form well-defined, air-stable, and colorless complexes with Cu(I) in aqueous solution. Concluding from X-ray structural data, electrochemical measurements, and an extensive network of equilibrium titrations, all three ligands form discrete Cu(I) complexes with 1:1 stoichiometry and are capable of buffering Cu(I) concentrations between 10−10 and 10−17 M. As most Cu(I) protein affinities have been obtained from competition experiments with bathocuproine disulfonate (BCS) or 2,2′-bicinchoninic acid (BCA), we further calibrated their Cu(I) stability constants against the MCL-series. To demonstrate the application of these reagents, we determined the Cu(I) binding affinity of CusF (logK = 14.3±0.1), a periplasmic metalloprotein required for the detoxification of elevated copper levels in E. coli. Altogether, this interconnected set of affinity standards establishes a reliable foundation that will facilitate the precise determination of Cu(I) binding affinities of proteins and small molecule ligands.

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Section: Discussionmentioning

confidence: 99%

Robust Affinity Standards for Cu(I) Biochemistry

et al. 2013

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“…Mintz and Delangle have exploited the tripodal architecture of a ligand to design a triantennary glycoside cluster system. 67 Experimental data have demonstrated that this system is also efficiently delivered to the hepatocytes. Furthermore, the glycoconjugate is not a Cu + chelator but the reduction by gluthatione converts it into an efficient chelator, which exhibits an affinity for Cu + as high as that of metallothioneins.…”

Section: Other Prochelatorsmentioning

confidence: 94%

Prochelator strategies for site-selective activation of metal chelators

Oliveri

Vecchio

2016

Journal of Inorganic Biochemistry

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“…The tripodal, disulfide-protected prochelator is reduced intracellularly to generate a high-affinity Cu(I) chelator (Figure 4e). [38,39]…”

Section: Passivating Metal Reactivity By Triggering Prochelatorsmentioning

confidence: 99%

Clawing back: broadening the notion of metal chelators in medicine

Franz

2013

Current Opinion in Chemical Biology

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The traditional notion of chelation therapy is the administration of a chemical agent to remove metals from the body. But formation of a metal-chelate can have biological ramifications that are much broader than metal elimination. Exploring these other possibilities could lead to pharmacological interventions that alter the concentration, distribution, or reactivity of metals in targeted ways for therapeutic benefit. This review highlights recent examples that showcase four general strategies of using principles of metal chelation in medicinal contexts beyond the traditional notion of chelation therapy. These strategies include altering metal biodistribution, inhibiting specific metalloenzymes associated with disease, enhancing the reactivity of a metal complex to promote cytotoxicity, and conversely, passivating the reactivity of metals by site-activated chelation to prevent cytotoxicity.

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A Sulfur Tripod Glycoconjugate that Releases a High‐Affinity Copper Chelator in Hepatocytes

Cited by 49 publications

References 28 publications

Robust Affinity Standards for Cu(I) Biochemistry

Robust Affinity Standards for Cu(I) Biochemistry

Prochelator strategies for site-selective activation of metal chelators

Clawing back: broadening the notion of metal chelators in medicine

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