The In-vitro Immunosuppressive Activity of the C-15-demethylated Metabolite of Fk-506 Is Governed By Ring-chain and Open-chain Tautomerism Effects

Lhoëst, Georges;Latinne, Dominique;Verbeeck, RK.;Maton, Nicole;Muthelet, P.
(1995) The Journal of Pharmacology and Experimental Therapeutics — Vol. 274, n° 2, p. 622-626 (1995)

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  • Lhoëst, GeorgesUCLouvain
    Author
  • Latinne, DominiqueUCLouvain
    Author
  • Verbeeck, RK.
    Author
  • Maton, NicoleUCLouvain
    Author
  • Muthelet, P.
    Author
Abstract
The FK-506 C-15-demethylated metabolite, isolated from human liver microsomes and identified by fast atom bombardment mass spectrometry and NMR spectroscopy, is under the influence of ring- and open-chain tautomerism effects as demonstrated by fast atom bombardment mass spectrometry. Ring- and open-chain tautomerism effects are strongly influencing the in vitro immunosuppressive potency expressed by the measure of the inhibition of the mixed lymphocyte reaction, as demonstrated by the clear differences observed in immunosuppressive activity between the FK-506 C-15-demethylated ring- and open-chain tautomeric conformations and depending on the tautomer-receptor specific interactions modulating the immunosuppressive activity of the FK-506 C-15-demethylated metabolite.
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Lhoëst, G., Latinne, D., Verbeeck, RK., Maton, N., & Muthelet, P. (1995). The In-vitro Immunosuppressive Activity of the C-15-demethylated Metabolite of Fk-506 Is Governed By Ring-chain and Open-chain Tautomerism Effects. The Journal of Pharmacology and Experimental Therapeutics, 274(2), 622-626. https://hdl.handle.net/2078.5/144800 (Original work published 1995)