title: Structure and activity of D-Pro14 melittin.
abstract: D-Pro14 melittin was synthesized to investigate the effect of increasing the angle of the bend in the hinge region between the helical segments of the molecule. Structural analysis by nuclear magnetic resonance indicated that, in methanol, the molecule consisted of two helices separated at Pro14, as in melittin. However, the two helices in D-Pro14 melittin were laterally displaced relative to each other by approximately 7 A, and in addition, there was a small rotation of the carboxyl-terminal helix relative to the amino-terminal helix around the long axis of the molecule. The peptide had less than 5% of the cytolytic activity of melittin. Modification of Arg22 with the 2,2,5,7,8-pentamethyl-chroman-6-sulphonyl (pmc) group restored hemolytic activity to close to that of unmodified melittin. Replacement of Arg22 with Phe was less effective in restoring hemolytic activity. Electron-paramagnetic resonance studies suggest that there is a positive correlation between hemolytic activity of the peptides and interaction with phospholipid bilayers.
authors.affiliation: CSIRO Health Sciences and Nutrition, Parkville Laboratory, Victoria, Australia. dean.hewish@csiro.au
authors.forename: Dean R
authors.initials: DR
authors.lastname: Hewish
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Werkmeister
authors.forename: Alan
authors.initials: A
authors.lastname: Kirkpatrick
authors.forename: Nicola
authors.initials: N
authors.lastname: Bartone
authors.forename: Su Ting
authors.initials: ST
authors.lastname: Liu
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Norton
authors.forename: Cyril
authors.initials: C
authors.lastname: Curtain
authors.forename: Donald E
authors.initials: DE
authors.lastname: Rivetta
mesh_terms: D016923:Cell Death / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008055:Lipids; D008223:Lymphoma / Q000473:pathology; D008555:Melitten / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D000432:Methanol; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D008055:Lipids; D008555:Melitten; D000432:Methanol