The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques.

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Groessl M, Bytzek A, Hartinger CG

The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques.

Electrophoresis. 2009 Aug;30(15):2720-7. doi: 10.1002/elps.200800745.

PubMed ID

19621374 [ View in PubMed

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Abstract

Transition metal-based drugs exhibit high affinity to the soft donors of human serum proteins, especially of the high-abundance protein HSA and of transferrin (Tf), whereas Ga(III) salts are known to bind to Tf and other iron-containing metalloproteins, thereby interfering with the iron metabolism. Herein, the utilization of CE-MS methods for studying the binding behavior of a therapeutic gallium nitrate formulation and the anticancer drug candidate Tris(8-oxyquinolinato)gallium(III) to Tf and HSA under simulated physiological conditions is described. Both the Ga(III) salt and the complex were found to bind to Tf exclusively in the presence of carbonate, however, at different kinetics and to a different extent. Fe(III) induces the release of the Ga ions due to the higher affinity constant and also prevents the Ga(III) species from accessing the iron-binding pockets of Tf. In contrast, only low affinity to HSA was observed and even when present at ca. 20-fold excess, the majority of the Ga was attached to Tf.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Gallium nitrate	Serotransferrin	Protein	Humans	Unknown	Binder	Details