Novel antimicrobial peptides from the venom of the eusocial bee Halictus sexcinctus (Hymenoptera: Halictidae) and their analogs.
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.
Monincová
Lenka
L
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, 16610, Prague 6, Czech Republic.
Budesínský
Milos
M
Slaninová
Jirina
J
Hovorka
Oldrich
O
Cvacka
Josef
J
Voburka
Zdenek
Z
Fucík
Vladimír
V
Borovicková
Lenka
L
Bednárová
Lucie
L
Straka
Jakub
J
Cerovský
Václav
V
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
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001514:Bee Venoms; D006460:Hemolysin Proteins