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Binding of Thalidomide to α 1-Acid Glycoprotein May be Involved in Its Inhibition of Tumor Necrosis Factor α Production

Benjamin E. Turk, Hongsi Jiang and Jun O. Liu
Proceedings of the National Academy of Sciences of the United States of America
Vol. 93, No. 15 (Jul. 23, 1996), pp. 7552-7556
Stable URL: http://www.jstor.org/stable/40071
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Binding of Thalidomide to α 1-Acid Glycoprotein May be Involved in Its Inhibition of Tumor Necrosis Factor α  Production
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Abstract

In addition to its well known sedative and teratogenic effects, thalidomide also possesses potent immunomodulatory and antiinflammatory activities, being most effective against leprosy and chronic graft-versus-host disease. The immunomodulatory activity of thalidomide has been ascribed to the selective inhibition of tumor necrosis factor α from monocytes. The molecular mechanism for the immunomodulatory effect of thalidomide remains unknown. To elucidate this mechanism, we synthesized an active photoaffinity label of thalidomide as a probe to identify the molecular target of the drug. Using the probe, we specifically labeled a pair of proteins of 43-45 kDa with high acidity from bovine thymus extract. Purification of these proteins and partial peptide sequence determination revealed them to be α 1-acid glycoprotein (AGP). We show that the binding of thalidomide photoaffinity label to authentic human AGP is competed with both thalidomide and the nonradioactive photoaffinity label at concentrations comparable to those required for inhibition of production of tumor necrosis factor α from human monocytes, suggesting that AGP may be involved in the immunomodulatory activity of thalidomide.

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