title: Antimicrobial peptides and their superior fluorinated analogues: structure-activity relationships as revealed by NMR spectroscopy and MD calculations.
abstract: The conformations of two synthetic pentapeptides with antimicrobial activity and their 4-fluorophenylalanine (Pff)-containing analogues (ArXArXAr-NH(2); Ar=Phe, Pff; X=Lys, Arg) have been studied. NMR experiments carried out both in aqueous fluoroalcohol solutions and SDS micelles permitted their interactions with membrane-like environments to be explored. WaterLOGSY experiments and Mn(2+)-based paramagnetic probes were also applied to assess their orientations with respect to the SDS micelles. In addition, pulse-field gradient (PFG) diffusion NMR spectroscopy studies were conducted, under different experimental conditions (i.e., concentration, temperature) to characterize the possible changes in the peptides' aggregation states as a putative critical factor for their antimicrobial activity. Finally, molecular dynamics simulations on a variety of conformations showed the intrinsic flexibility of these peptides in both aqueous solutions and membrane-mimetic systems.
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: Martina
authors.initials: M
authors.lastname: Palomino-Schätzlein
authors.forename: Francisco
authors.initials: F
authors.lastname: Corzana
authors.forename: Cecilia
authors.initials: C
authors.lastname: Andreu
authors.forename: Rodrigo J
authors.initials: RJ
authors.lastname: Carbajo
authors.forename: Marcellí
authors.initials: M
authors.lastname: del Olmo
authors.forename: Angeles
authors.initials: A
authors.lastname: Canales-Mayordomo
authors.forename: Antonio
authors.initials: A
authors.lastname: Pineda-Lucena
authors.forename: Gregorio
authors.initials: G
authors.lastname: Asensio
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D009842:Oligopeptides; D012996:Solutions; D014867:Water; D012967:Sodium Dodecyl Sulfate