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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Covalent binding of a bucillamine derivative with albumin in sera from healthy subjects and patients with various diseases.

PURPOSE: To investigate the difference of pharmacokinetics of thiol-containing drugs in various disease states, we studies the covalent binding of SA3786, a bucillamine derivative, with proteins in patient serum compared with that in healthy serum. METHODS: Sera from healthy volunteers and patients of various diseases were supplied by the Japanese Red Cross Kumamoto Hospital. For the formation of conjugate experiments, SA3786 was added to a final concentration of 7 x 10(-4)M. After 6 h incubation at 37 degrees C, HPLC analysis of 5 microliters aliquots of each sample was performed using a column of N-methylpyridinium polymer (4VP-Me). RESULTS: The extent of HSA-SA3786 conjugate formation was found to be lower in the sera from healthy volunteers (control) than those from patients of various diseases. Especially high reactivity with SA3786 was observed in sera from rheumatic patients and hepatic patients. With the exception of the fraction of mercaptoalbumin (fHMA), none of the parameters showed a good correlation with conjugate formation. CONCLUSIONS: The parameter fHMA must be considered to be one of the most important factors in formation of conjugates between plasma protein and thiol compounds. However, other factors may be involved in addition to fHMA although the nature of these factors is not clear.[1]


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