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.
Than
Chistopher Trong-Linh
CT
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Ferguson
Glen Allen
GA
Raghavachari
Krishnan
K
D002087:Butyrates / Q000737:chemistry*; D003500:Cyclization; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
D002087:Butyrates; D010455:Peptides; D000644:Quaternary Ammonium Compounds; C547303:trimethylammonium butyric acid; D008239:Lysine