MOLECULAR RECOGNITION IN ALLERGIC CONTACT-DERMATITIS TO NATURAL-PRODUCTS

The chemical stuctures of natural skin allergens is discussed: the majority is electrophilic or “proelectrophilic” (i.e. they can be transformed in the skin into electrophiles. A number of natural and model skin allergens (or haptens), in particular optically active β-substituted-α-methylene-λ+03BB;-butyrolactones such as tulipalins B, have been synthesized and their allergenic activity tested in the guinea pig. A remarkable enantiospecificity of the in vivo response is noted when the chiral center is close to the protein site of attack, the α-methylene group. Use of an in vitro model, reaction of selected haptens with a dipeptide, BOC-Cys (SH)-Ala-OMe, shows parallelism between the stereoselectivity of the Michael addition and enantiospecificity of the in vivo reaction, allowing some reasonable predictions to be made. © 1990 De Gruyter