title: D-form KLKLLLLLKLK-NH2peptide exerts higher antimicrobial properties than its L-form counterpart via an association with bacterial cell wall components.
abstract: The antimicrobial peptide KLKLLLLLKLK-NH2was developed based on sapesin B, and synthesized using D-amino acids. Biochemical properties of the D-form and L-form KLKLLLLLKLK-NH2peptides were compared. In order to limit the effects due to bacterial resistance to proteolysis, antimicrobial activities of the peptides were evaluated after short-term exposure to bacteria. D-form KLKLLLLLKLK-NH2exhibited higher antimicrobial activities than L-form KLKLLLLLKLK-NH2against bacteria, including Staphylococcus aureus and Escherichia coli. In contrast, both the D-form and L-form of other antimicrobial peptides, including Mastoparan M and Temporin A, exhibited similar antimicrobial activities. Both the D-form KLKLLLLLKLK-NH2and L-form KLKLLLLLKLK-NH2peptides preferentially disrupted S. aureus-mimetic liposomes over mammalian-mimetic liposomes. Furthermore, the D-form KLKLLLLLKLK-NH2increased the membrane permeability of S. aureus more than the L-form KLKLLLLLKLK-NH2. Thus suggesting that the enhanced antimicrobial activity of the D-form was likely due to its interaction with bacterial cell wall components. S. aureus peptidoglycan preferentially inhibited the antimicrobial activity of the D-form KLKLLLLLKLK-NH2relative to the L-form. Furthermore, the D-form KLKLLLLLKLK-NH2showed higher affinity for S. aureus peptidoglycan than the L-form. Taken together, these results indicate that the D-form KLKLLLLLKLK-NH2peptide has higher antimicrobial activity than the L-form via a specific association with bacterial cell wall components, including peptidoglycan.
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Manabe
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawasaki
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; D008081:Liposomes; D009842:Oligopeptides; D010455:Peptides; D010457:Peptidoglycan; D011506:Proteins; D014862:Wasp Venoms; C403864:mastoparan M; C096884:nysyl-leucyl-lysyl-leucyl-leucyl-leucyl-leucyl-leucyl-lysyl-leucyl-lysinamide; C080667:sapecin B protein, Sarcophaga peregrina; C104501:temporin