title: Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics.
abstract: The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.
authors.affiliation: Biomedical Science Research Complex University of St Andrews, BSRC North Haugh St Andrews KY16 9ST UK.
authors.forename: Emilia
authors.initials: E
authors.lastname: Oueis
authors.affiliation: Marine Biodiscovery Centre, Department of Chemistry University of Aberdeen Old Aberdeen AB24 3UE UK.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
authors.affiliation: Biomedical Science Research Complex University of St Andrews, BSRC North Haugh St Andrews KY16 9ST UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Westwood
authors.affiliation: Biomedical Science Research Complex University of St Andrews, BSRC North Haugh St Andrews KY 16 9 ST UK; State Key Laboratory of Biotherapy Sichuan University China.
authors.forename: James H
authors.identifier: 0000-0001-6744-5061
authors.initials: JH
authors.lastname: Naismith
keywords: Biotransformation; Cyanobactin; Cyclische Peptide; Peptidmimetika; Triazol