title: Structural glance into a novel anti-staphylococcal peptide.
abstract: Novel antimicrobial peptides are valuable molecules for developing anti-infective drugs to counteract the contemporary spread of microbial drug-resistance. Here we focus on a novel peptide (RKWVWWRNR-NH2) derived from the fragment 107-115 of the human lysozyme that displays a 20-fold increase in anti-staphylococcal activity. The conformational analysis of this peptide and its interaction with model lipidic phases-as assayed by circular dichroism and fluorescence spectroscopy-show a noteworthy spectral change, which might be related to its anti-staphylococcal activity. The secondary structure of peptide [K(108)W(111)] 107-115 hLz was dramatically affected through a single substitution at position 111 (Ala by Trp). Therefore, this conformational change might improve the interaction of the novel peptide with the bacterial plasma membrane. These results highlight the role of peptide secondary structure and the distribution of polar/nonpolar residues for the effective interaction of this peptide with the bacterial plasma membrane, a key step for triggering its lethal effect. This knowledge may contribute to the rational design of a new generation of antimicrobial peptides with increased efficacy developed from natural sources by simple screening tools.
authors: Department of Biological Chemistry and Institute of Biochemistry and Biophysics (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina; Therapeutic Peptides Research and Development Laboratory, Chemo-Romikin, Carlos Villate 5148, B1605AXL, Buenos Aires, Argentina.
authors: N B
authors: NB
authors: Iannucci
authors: L M
authors: LM
authors: Curto
authors: F
authors: F
authors: Albericio
authors: O
authors: O
authors: Cascone
authors: J M
authors: JM
authors: Delfino
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D013050:Spectrometry, Fluorescence; D013210:Staphylococcus / Q000187:drug effects*; D014867:Water / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D014867:Water
keywords: cationic antimicrobial peptides; circular dichroism; conformation; fluorescence; human lysozyme; phospholipid detergent micelles