title: Novel antimicrobial peptides from the venom of the eusocial bee Halictus sexcinctus (Hymenoptera: Halictidae) and their analogs.
abstract: Two novel antimicrobial peptides, named halictines, were isolated from the venom of the eusocial bee Halictus sexcinctus. Their primary sequences were established by ESI-QTOF mass spectrometry, Edman degradation and enzymatic digestion as Gly-Met-Trp-Ser-Lys-Ile-Leu-Gly-His-Leu-Ile-Arg-NH2 (HAL-1), and Gly-Lys-Trp-Met-Ser-Leu-Leu-Lys-His-Ile-Leu-Lys-NH2 (HAL-2). Both peptides exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria but also noticeable hemolytic activity. The CD spectra of HAL-1 and HAL-2 measured in the presence of trifluoroethanol or SDS showed ability to form an amphipathic alpha-helical secondary structure in an anisotropic environment such as bacterial cell membrane. NMR spectra of HAL-1 and HAL-2 measured in trifluoroethanol/water confirmed formation of helical conformation in both peptides with a slightly higher helical propensity in HAL-1. Altogether, we prepared 51 of HAL-1 and HAL-2 analogs to study the effect of such structural parameters as cationicity, hydrophobicity, alpha-helicity, amphipathicity, and truncation on antimicrobial and hemolytic activities. The potentially most promising analogs in both series are those with increased net positive charge, in which the suitable amino acid residues were replaced by Lys. This improvement basically relates to the increase of antimicrobial activity against pathogenic Pseudomonas aeruginosa and to the mitigation of hemolytic activity.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, 16610, Prague 6, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Monincová
authors.forename: Milos
authors.initials: M
authors.lastname: Budesínský
authors.forename: Jirina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Oldrich
authors.initials: O
authors.lastname: Hovorka
authors.forename: Josef
authors.initials: J
authors.lastname: Cvacka
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Voburka
authors.forename: Vladimír
authors.initials: V
authors.lastname: Fucík
authors.forename: Lenka
authors.initials: L
authors.lastname: Borovicková
authors.forename: Lucie
authors.initials: L
authors.lastname: Bednárová
authors.forename: Jakub
authors.initials: J
authors.lastname: Straka
authors.forename: Václav
authors.initials: V
authors.lastname: Cerovský
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001514:Bee Venoms / Q000737:chemistry*; D001516:Bees / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D006460:Hemolysin Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001514:Bee Venoms; D006460:Hemolysin Proteins