title: Quaternary amine-induced peptide degradation via cyclization.
abstract: 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.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Chistopher Trong-Linh
authors.initials: CT
authors.lastname: Than
authors.forename: Glen Allen
authors.initials: GA
authors.lastname: Ferguson
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavachari
mesh_terms: D002087:Butyrates / Q000737:chemistry*; D003500:Cyclization; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
chemical_list: D002087:Butyrates; D010455:Peptides; D000644:Quaternary Ammonium Compounds; C547303:trimethylammonium butyric acid; D008239:Lysine