title: The in vitro immunosuppressive activity of the C15-demethylated metabolite of FK-506 is governed by ring- and open-chain tautomerism effects.
abstract: The FK-506 C15-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 C15-demethylated ring- and open-chain tautomeric conformations and depending on the tautomer-receptor specific interactions modulating the immunosuppressive activity of the FK-506 C15-demethylated metabolite.
authors.affiliation: Department of Pharmaceutical Sciences, UCL, Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Lhoëst
authors.forename: R K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: N
authors.initials: N
authors.lastname: Maton
authors.forename: P
authors.initials: P
authors.lastname: Muthelet
authors.forename: D
authors.initials: D
authors.lastname: Latinne
mesh_terms: D000328:Adult; D003640:Dealkylation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus