title: Synthesis and characterization of cyclic peptides that are β-helical in trifluoroethanol.
abstract: We show that three designed cyclic d,l-peptides are β-helical in TFE-a solvent in which the archetypal β-helical peptide, gA, is unstructured. This result represents an advance in the field of β-helical peptide foldamers and a step toward achieving β-helical structure under a broad range of solvent conditions. We synthesized two of the three peptides examined using an improved variant of our original CBC strategy. Here, we began with a commercially available PEG-PS composite resin prefunctionalized with the alkanesulfonamide 'SCL' linker and preloaded with glycine. Our new conditions avoided C-terminal epimerization during the CBC step and simplified purification. In addition, we present results to define the scope and limitations of our CBC strategy. These methods and observations will prove useful in designing additional cyclic β-helical peptides for applications ranging from transmembrane ion channels to ligands for macromolecular targets. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
authors.affiliation: Division of Chemistry, Naval Research Laboratory, Washington, DC, 20375-5342, USA.
authors.forename: Kenan P
authors.initials: KP
authors.lastname: Fears
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Photiadis
authors.forename: John L
authors.initials: JL
authors.lastname: Kulp
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Clark
mesh_terms: D003500:Cyclization; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014270:Trifluoroethanol / Q000737:chemistry*
chemical_list: D010456:Peptides, Cyclic; D014270:Trifluoroethanol
keywords: NMR spectroscopy; circular dichroism; gramicidin A; vibrational circular dichroism; β-helix