Spectroscopic Characterization of Copper(II) Binding to the Immunosuppressive Drug Mycophenolic Acid

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• 作者：Christopher E. Jones ; Paul J. Taylor ; Alastair G. McEwan ; and Graeme R. Hanson
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：July 26, 2006
• 年：2006
• 卷：128
• 期：29
• 页码：9378 - 9386
• 全文大小：179K
• 年卷期：v.128,no.29(July 26, 2006)
• ISSN：1520-5126

文摘

Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressiveagent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinalside effects which can range in severity. One mechanism by which MPA causes gastropathy may involvea direct interaction between the drug and gastric phospholipids. To combat this interaction we haveinvestigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathyassociated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show thatCu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The coppercomplex formed is stable in solution as assessed by mass spectrometry and ¹H NMR diffusion experiments.Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) toamino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer toserum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility thatcopper complexes of MPA may be useful in a therapeutic situation.