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

Abstract

Induction of a state of tolerance (hyposensitization) in alantolactone-sensitized guinea pigs was attempted by subcutaneous injections of S-(dihydroalantolacton-10-yl)- l-cysteinyl- l-alanine methyl ester 7, N-acetyl- l-cysteinyl- l-alanine 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 μg. 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.