title: Capped acyclic permutants of the circular protein kalata B1.
abstract: The cyclotides are a family of head-to-tail cyclized peptides that display exceptionally high stability and a range of biological activities. Acyclic permutants that contain a break in the circular backbone have been reported to be devoid of the haemolytic activity of the prototypic cyclotide kalata B1, but the potential role of the charges at the introduced termini in this loss of membraneolytic activity has not been fully determined. In this study, acyclic permutants of kalata B1 with capped N- and C-termini were synthesized and found to adopt a native fold. These variants were observed to cause no measurable lysis of erythrocytes, strengthening the connection between backbone cyclization and haemolytic activity.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld. 4072, Australia.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Simonsen
authors.forename: Norelle L
authors.initials: NL
authors.lastname: Daly
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D047169:Cyclotides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D019666:Rubiaceae / Q000737:chemistry; D012756:Sheep
chemical_list: D047169:Cyclotides; D004220:Disulfides; D010940:Plant Proteins; D011506:Proteins; C091930:kalata B1; D003545:Cysteine