title: Synthesis and conformational analysis of an expanded cyclic ketoxime-hexapeptide.
abstract: In this work the synthesis of a linear hexapeptide with a hydroxylamine functionality at the N-terminus and a ketone instead of the carboxylic acid at the C-terminus is described. Cyclization by ketoxime formation yields the 19-membered ring-expanded cyclic hexapeptide cyclo[Goly-Val-Ala-Pro-Leu-Kly] which adopts a main conformer with two intramolecular hydrogen bonds. The hydrolytic stability of a ketoxime lies between the inert amide and the labile imine. The substitution of an amide bond for an iminium bond transforms the irreversible macrocyclization into a reversible process, but macrocyclic imines are difficult to isolate because they are prone to hydrolysis. The enhanced chemical stability of the ketoxime justifies its application in ligation protocols. The detailed NMR analysis of a ketoxime linkage presented here identifies its local conformational preferences in a constrained peptide environment.
authors.affiliation: Institute of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße, 35032, Marburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lamping
authors.affiliation: Institute of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße, 35032, Marburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Grell
authors.affiliation: Institute of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße, 35032, Marburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Geyer
mesh_terms: D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D009842:Oligopeptides / Q000138:chemical synthesis*; D010091:Oximes / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011487:Protein Conformation
chemical_list: D009842:Oligopeptides; D010091:Oximes; D010456:Peptides, Cyclic
keywords: NMR; conformation; cyclization; oxime; peptide