Methionine thioether

Mozier NM, McConnell KP, Hoffman JL. 1988. S-Adenosyl-L-methionine thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism. J Biol Chem 263 4527-4531. 

The guanidino group of Arg is usually protected by protonation under normal reaction conditions due to its strongly basic character. The indole ring of Trp usually does not require any protecting measures. The broad variety of synthetic conditions permits the incorporation of unprotected Trp. The methionine thioether group usually does not cause severe comphcations during peptide synthesis. 

This side reaction is relatively innocuous because the by-product is irreversibly bound to the polymer and only the yield is affected not the purity of the synthetic peptide. More disturbing is the succinimide ring formation at aspartyl residues exposed to HF. Alkylation of the indole ring in tryptophan, the phenolic side chain in tyrosine and the sulfur atom in methionine must be suppressed by the addition of scavengers. The often appUed anisole is less than unequivocal in this role it can be the source of methyl groups which convert the methionine thioether to a tertiary sulfonium derivative. The acid stable thioanisole seems to be a better scavenger. 

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