We studied the stability of Fmoc, Trt, and Boc protecting groups under a variety of electrospray ionization (ESI) (+) or (‒) conditions in ACN, MeOH, TFE, and DMF media or their mixtures with water in the presence of either acidic or basic additives, or without any additives. Generally, all the studied protecting groups remained stable under a majority of the studied conditions. We found that the cleavage of the Fmoc protecting group is possible under very mild conditions: aqueous DMF containing approximately 17% of water in the presence of TEA. The collected data will likely find usage in various ESI-MS and HPLC-MS applications, as well as in the chemistry of protecting groups and electrospray-mediated peptide synthesis.
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