Mechanism of the antigen formation of carvone and related alpha,beta-unsaturated ketones

In the present study, the mechanism for the antigen formation of alpha, bet a -unsaturated ketones was investigated. A series of analogues of carvone ( (SR)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivi ty and with retained overall structure or with retained reactivity and alte red three-dimensional structure were synthesized. These analogues were test ed for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((SR)-5-isopropyl-2-methyl-2-cyclohexen- 1-one). N o cross-reactions were observed for analogues 1 ((2R,SR)-5-isopropenyl-2-me thyl cyclohexanone) and 4 ((5R:)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1 -one). Both those compounds also failed to induce sensitization. These find ings demonstrate that alpha, beta -unsaturated ketones form antigens after a nucleophilic attack at the beta -carbon with soft nucleophiles such as th iol in cysteine and not with the formation of a Schiff's base after a nucle ophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermo re, no cross-reactivity was observed between R- and S-carvone indicating th e importance of the 3-dimensional structure of haptens (and antigens) in T- cell recognition. The analogues were also tested for cross-reactivity on pa tients allergic to carvone. The results from the animal study were confirme d.