Methionine-Containing Peptides: Avoiding Secondary Reactions in the Final Global Deprotection.

ABSTRACT: The solid-phase synthesis of Met-containing peptides using a fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (tBu) protection scheme is inevitably accompanied by two stubborn side reactions, namely, oxidation and S-alkylation (tert-butylation), which result in the formation of Met(O) and sulfonium salt impurities of the target peptide, respectively. These two reactions are acid-catalyzed, and they occur during the final trifluoroacetic (TFA)-based acidolytic cleavage step. Herein, we developed two new cleavage solutions that eradicate the oxidation and reduce S-alkylation. TFA-anisole-trimethylsilyl chloride (TMSCl)-Me₂S-triisopropylsilane (TIS) containing 1 mg of triphenyl phosphine per mL of solution was the optimal mixture for Cys-containing pept

SUBMITTER: Nandhini KP 

PROVIDER: S-EPMC10157837 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature