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 FK-506 C-15-demethylated metabolite, isolated from human liver mic rosomes and identified by fast atom bombardment mass spectrometry and NMR spectroscopy, is under the influence of ring- and open-chain tauto merism effects as demonstrated by fast atom bombardment mass spectrome try. Ring- and open-chain tautomerism effects are strongly influencing the in vitro immunosuppressive potency expressed by the measure of th e inhibition of the mixed lymphocyte reaction, as demonstrated by the clear differences observed in immunosuppressive activity between the F K-506 C-15-demethylated ring- and open-chain tautomeric conformations and depending on the tautomer-receptor specific interactions modulatin g the immunosuppressive activity of the FK-506 C-15-demethylated metab olite.