The alkylation of cysteine residue by different classes of carbonium ions, derived from the cleavage of side chain protective groups in anhydrous HF, was investigated. It was found that side chain protection as beta-2,4-dimethylpent-3-yl ester (Dmp) or 2,4-dimethylpent-3-yloxycarbonyl (Doc) groups resulted in more than seven-fold lower level of alkylated byproducts. This makes Dmp and Doc protection of amino acid side chain during solid phase synthesis particularly valuable in the synthesis of peptides containing cysteine residues or other functional groups prone to alkylation by carbonium ions.