title: Structural framework for the modulation of the activity of the hybrid antibiotic peptide cecropin A-melittin [CA(1-7)M(2-9)] by Nε-lysine trimethylation.
abstract: The 3D structures of six linear pentadecapeptides derived from the cecropin A-melittin antimicrobial peptide CA(1-7)M(2-9) [KWKLFKKIGAVLKVL-NH(2)] have been studied. These analogues are modified by ε-NH(2) trimethylation of one or more lysine residues and showed variation in both antimicrobial and cytotoxic activities, depending on the number and position of modified lysines. Since it is expected that these peptides will display a strong conformational ordering when in contact with membranes, we have investigated their structure on the basis of the data extracted from NMR experiments performed in membrane-mimetic environments. We show that inclusion of N(ε)-trimethylated lysine residues induces a certain degree of structural flexibility, while preserving to a variable extent a largely α-helical structure. In addition, peptide orientation with respect to SDS micelles has been explored by detection of the intensity changes of peptide NMR signals upon addition of a paramagnetic probe (Mn(2+) ions).
authors.affiliation: Departamento de Biología Físico-Química, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Díaz
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: de la Torre
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Reyes
authors.forename: Luis
authors.initials: L
authors.lastname: Rivas
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008823:Micelles; D008958:Models, Molecular; D011487:Protein Conformation; D055550:Protein Stability; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D008823:Micelles; C435762:cecropin A(1-7)melittin(2-9); D012967:Sodium Dodecyl Sulfate; D008239:Lysine