Synthesis of FMOC-Protected S -arylcysteines and Modified Keratin Sequence Peptides as Specific Epitopes as Immunogens

• Published in: Polycyclic aromatic compounds 2002-01, Vol.22 (3-4), p.239-248
• Main Authors: Nam, Tae-Gyu, Sangaiah, R., Gold, Avram, Lacks, Gregory D., Nylander-French, Leena A., French, John E.
• Format: Article
• Language: English
• Subjects: Fmoc-protected Modified Cysteines; Keratin Adducts Of Arene Oxides; Protein Adducts; S -arylcysteines
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406630290026885

The sulfhydryl group of cysteine residues is a site for the adduction of ultimate carcinogenic arene oxide metabolites to the proteins keratin 1 and keratin 10, dominant proteins of the squame. The putative cysteine adducts are: S -phenylcysteine, from benzene oxide and S -(1-naphthyl)- and S -(2-naphthyl)cysteine from naphthalene-1,2-oxide. In developing ELISAs for monitoring dermal exposures, we have embarked on synthesis of adducted head sequences GGRFSS(C*)GG (keratin 1) and GGGG(C*)GGGGG (keratin 10) by 9-fluorenyl-methoxycarbonyl chemistry to use in raising epitope-specific antibodies. Synthesis of the FMOC-protected cysteines was based on addition of arylthiols to 2-acetamidoacrylic acid, to give S -arylmercapturic acids. Removal of the N -acetyl group was accomplished quantitatively by extended refluxing in 1:1 t -butanol/concentrated HCl. FMOC derivatization of the S -arylcysteines was accomplished by a published procedure, modified because of the low solubility. The oligopeptides (C* = S -phenylcysteinyl residue) have been synthesized and characterized.