Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid

Jones, C. E., Taylor, P. J., McEwan, A. G. and Hanson, G. R. (2006) Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid. Journal of The American Chemical Society, 128 29: 9378-9386. doi:10.1021/ja057651l


Author Jones, C. E.
Taylor, P. J.
McEwan, A. G.
Hanson, G. R.
Title Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid
Journal name Journal of The American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1021/ja057651l
Volume 128
Issue 29
Start page 9378
End page 9386
Total pages 9
Place of publication Washington
Publisher Amer Chemical Soc
Language eng
Subject C1
250302 Biological and Medical Chemistry
780105 Biological sciences
Abstract Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric phospholipids. To combat this interaction we have investigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathy associated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show that Cu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The copper complex formed is stable in solution as assessed by mass spectrometry and H-1 NMR diffusion experiments. Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) to amino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer to serum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility that copper complexes of MPA may be useful in a therapeutic situation.
Keyword Chemistry, Multidisciplinary
Electron-paramagnetic-resonance
Inosine Monophosphate Dehydrogenase
Nonsteroidal Antiinflammatory Drugs
Superoxide-dismutase Activity
Ascidian Lissoclinum-patella
Renal-transplant Patients
Bovine Serum-albumin
Crystal-structure
Mofetil
Sodium
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 19:15:22 EST