title: Enhanced antimicrobial activity of novel synthetic peptides derived from vejovine and hadrurin.
abstract: BACKGROUND
  Microbial antibiotic resistance is a challenging medical problem nowadays. Two scorpion peptides displaying antibiotic activity: hadrurin and vejovine were taken as models for the design of novel shorter peptides with similar activity.
  
  
  METHODS
  Using the standard Fmoc-based solid phase synthesis technique of Merrifield twelve peptides (18 to 29 amino acids long) were synthesized, purified and assayed against a variety of multi-drug resistant Gram-negative bacteria from clinical isolates. Hemolytic and antiparasitic activities of the peptides and their possible interactions with eukaryotic cells were verified. Release of the fluorophore calcein from liposomes treated with these peptides was measured.
  
  
  RESULTS
  A peptide with sequence GILKTIKSIASKVANTVQKLKRKAKNAVA), and three analogs: Δ(Α29), Δ(K12-Q18; Ν26-Α29), and K4N Δ(K12-Q18; Ν26-Α29) were shown to inhibit the growth of Gram-negative (E. coli ATCC25922) and Gram-positive bacteria (S. aureus), as well as multi-drug resistant (MDR) clinical isolated. The antibacterial and antiparasitic activities were found with peptides at 0.78 to 25μM and 5 to 25μM concentration, respectively. These peptides have low cytotoxic and hemolytic activities at concentrations significantly exceeding their minimum inhibitory concentrations (MICs), showing values between 40 and 900μM for their EC50, compared to the parent peptides vejovine and hadrurin that at the same concentration of their MICs lysed more than 50% of human erythrocytes cells.
  
  
  CONCLUSIONS
  These peptides promise to be good candidates to combat infections caused by Gram-negative bacteria from nosocomial infections.
  
  
  CONCLUSIONS
  Our results confirm that well designed synthetic peptides can be an alternative for solving the lack of effective antibiotics to control bacterial infections.
authors: Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Autonóma de México, Avenida Universidad, México.
authors: Lorenzo
authors: L
authors: Sánchez-Vásquez
authors: Jesus
authors: J
authors: Silva-Sanchez
authors: Juana Maria
authors: JM
authors: Jiménez-Vargas
authors: Adela
authors: A
authors: Rodríguez-Romero
authors: Carlos
authors: C
authors: Muñoz-Garay
authors: Maria C
authors: MC
authors: Rodríguez
authors: Georgina B
authors: GB
authors: Gurrola
authors: Lourival D
authors: LD
authors: Possani
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000254:growth & development*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010962:Plasmodium berghei / Q000254:growth & development*; D012604:Scorpion Venoms; D013211:Staphylococcus aureus / Q000254:growth & development*
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D010455:Peptides; D012604:Scorpion Venoms; C414302:hadrurin; C557215:vejovine