Suppression of the skin response to alantolactone in alantolactone-sensitized guinea pigs treated with N-acetyl-L-cysteinyl-L-alanine methyl ester

Induction of a state of tolerance (hyposensitization) in alantolactone-sensitized guinea pigs was attempted by subcutaneous injections of S-(dihydroalantolacton-lO-yl)-L-cysteinyl-L-alanine methyl ester 7, N-acetyl-L-cysteinyl-Lalanine methyl ester 11 or N-acetyl-L-cysteine. Compound 7 was prepared by addition of N-benzyloxycarbonyl-L-cysteinyl- L-alanine methyl ester 5 to alantolactone, followed by the removal of the Z-group. Dipeptide 11 was obtained from N-acetyl-S-ethylcarbamoyl-L-cysteinyl-L-alanine methyl ester. Treatment of dipeptide 5 with HBr-AcOH mixture afforded mainly the S-acetyl derivative 10, from which dipeptide 11 was also obtained. Biological assays showed that the alantolactone- adduct 7 or N-acetyl-L-cysteine did not significantly modify the positive skin response to alantolactone in alantolactone-sensitive guinea pigs. In marked contrast, dipeptide 11 significantly decreased the skin reaction to alantolactone tested at either 0.25 or 0.08 jJ-g. Control animals did not show skin responses to alantolactone neither after treatment with dipeptides 7,11 or N-acetyl-L-cysteine. The data suggest that dipeptide 11 is an efficient and non-toxic tolerogen in the case of guinea pigs sensitized to alantolactone.