Nuclear magnetic resonance studies of the binding of captopril and penicillamine by serum albumin.

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Keire DA, Mariappan SV, Peng J, Rabenstein DL

Nuclear magnetic resonance studies of the binding of captopril and penicillamine by serum albumin.

Biochem Pharmacol. 1993 Sep 14;46(6):1059-69.

PubMed ID

8216349 [ View in PubMed

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Abstract

The metabolism of the thiol-containing drugs penicillamine (beta,beta-dimethylcysteine) and captopril (D-3-mercapto-2-methylpropanoyl-L-proline) involves the formation of mixed disulfides, including mixed disulfides with serum albumin. The reactions of penicillamine and captopril with serum albumin in aqueous solution and in intact human blood plasma have been studied by 500 MHz 1H NMR spectroscopy. Penicillamine was found to react rapidly at the albumin-cysteine mixed disulfide bond to form penicillamine-cysteine mixed disulfide and to react more slowly at other albumin disulfide bonds. The amino acid cysteine was found to react with albumin by the same two pathways. In contrast, captopril rapidly associates with albumin to form noncovalent albumin-captopril complexes. Exchange of captopril between its free and noncovalently bound forms takes place on the NMR time scale. On a longer time scale, captopril reacts with albumin by thiol/disulfide interchange reactions. Noncovalently bound captopril displaced lactate from its albumin binding sites, both in aqueous solution and in human plasma. The results demonstrate that 1H NMR is a useful method for characterizing the state of drug molecules in human plasma and for detecting and monitoring perturbations by drugs of delicately balanced binding equilibria involving endogenous small molecules and macromolecules in plasma.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Captopril	Serum albumin	Protein	Humans	No	Other/unknown	Details