Quaternary amine-induced peptide degradation via cyclization.

In this study, we investigated intramolecular cyclizations in peptides containing quaternary amines. Two types of cyclization reactions are studied: (a) those involving a trimethylammonium butyric acid (TMAB) charge tag and (b) those involving trimethylated lysine. Both types of reactions result in the release of trimethylamine via an S(N)2 mechanism involving a lone pair of electrons on the oxygen or nitrogen. In the case of the TMAB charge tag cyclization, the oxygen attack mechanism leading to a five-membered ring is the preferred pathway. In the trimethylated lysine cyclizations, the preferred pathway involves the nitrogen nucleophile resulting in the formation of a six-membered ring. The similarities and differences between the two reactions are analyzed.