1: J Pharmacol Exp Ther 1995 Aug;274(2):622-6
The in vitro immunosuppressive activity of the C15-demethylated metabolite
of FK-506 is governed by ring- and open-chain tautomerism effects.
Lhoest G, Verbeeck RK, Maton N, Muthelet P, Latinne D
Department of Pharmaceutical Sciences, UCL, Brussels, Belgium.
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.
PMID: 7543569, UI: 95363673