title: Twisted amide electrophiles enable cyclic peptide sequencing.
abstract: There is an ever-increasing interest in synthetic methods that not only enable peptide macrocyclization, but also facilitate downstream application of the synthesized molecules. We have found that aziridine amides are stereoelectronically attenuated in a macrocyclic environment such that non-specific interactions with biological nucleophiles are reduced or even shut down. The electrophilic reactivity, revealed at high pH, enables peptide sequencing by mass spectrometry, which will further broaden the utility of aziridine amide-containing libraries of macrocycles.
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6, Canada. ayudin@chem.utoronto.ca.
authors.forename: Serge
authors.initials: S
authors.lastname: Zaretsky
authors.forename: Vishal
authors.initials: V
authors.lastname: Rai
authors.forename: Gerald
authors.initials: G
authors.lastname: Gish
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Forbes
authors.forename: Michael
authors.initials: M
authors.lastname: Kofler
authors.forename: Joy C Y
authors.initials: JC
authors.lastname: Yu
authors.forename: Joanne
authors.initials: J
authors.lastname: Tan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hickey
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Andrei K
authors.initials: AK
authors.lastname: Yudin
mesh_terms: D000577:Amides / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry; D004583:Electrons; D006868:Hydrolysis; D007659:Ketones / Q000737:chemistry; D013058:Mass Spectrometry; D010456:Peptides, Cyclic / Q000737:chemistry*; D020539:Sequence Analysis, Protein
chemical_list: D000577:Amides; D001388:Aziridines; D007659:Ketones; D010456:Peptides, Cyclic; C033132:aziridine