Synthesis of S-aryl-D,L-cysteines and incorporation into keratin sequences

摘要

Although there is a significant potential for benzene and naphthalene toxicity through dermal exposure in occupational setting, no satisfactory method for quantitation of dermal dose has been developed nor have possible mechanisms of action been extensively investigated. The epoxide metabolites of both aromatics form protein adducts, targeting the nucleophilic sulfhydryl group of cysteine residues. In dermal exposures, the most accessible cysteines will be residues in the head region of the kerain proteins K1 and K10, which are associated in intermediate filaments in stratum corneum. Keratin adducts may serve as biomarkers and may also mediate dermal toxicity. Benzene oxide is symmetrical and only a single product, S-phenylcysteine, is generated by nucleophilic addition to the cysteine sulfhydryl group. The C1-C2 bond of naphthalene is epoxidized and the 1,2-oxide may undergo nucleophilic attack at either position 1 or 2 to yield S-(1-naphthyl)cysteine and S-(2-naphthyl)cysteine, respectively.