title: Effect of hydrocarbon stapling on the properties of α-helical antimicrobial peptides isolated from the venom of hymenoptera.
abstract: The impact of inserting hydrocarbon staples into short α-helical antimicrobial peptides lasioglossin III and melectin (antimicrobial peptides of wild bee venom) on their biological and biophysical properties has been examined. The stapling was achieved by ring-closing olefin metathesis, either between two S-2-(4'-pentenyl) alanine residues (S (5)) incorporated at i and i + 4 positions or between R-2-(7'-octenyl) alanine (R (8)) and S (5) incorporated at the i and i + 7 positions, respectively. We prepared several lasioglossin III and melectin analogs with a single staple inserted into different positions within the peptide chains as well as analogs with double staples. The stapled peptides exhibited a remarkable increase in hemolytic activity, while their antimicrobial activities decreased. Some single stapled peptides showed a higher resistance against proteolytic degradation than native ones, while the double stapled analogs were substantially more resistant. The CD spectra of the singly stapled peptides measured in water showed only a slightly better propensity to form α-helical structure when compared to native peptides, whereas the doubly stapled analogs exhibited dramatically enhanced α-helicity.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6 16610, Czech Republic.
authors.forename: Hubert
authors.initials: H
authors.lastname: Chapuis
authors.forename: Jiřina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Lucie
authors.initials: L
authors.lastname: Bednárová
authors.forename: Lenka
authors.initials: L
authors.lastname: Monincová
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Václav
authors.initials: V
authors.lastname: Čeřovský
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001514:Bee Venoms / Q000737:chemistry*; D001516:Bees / Q000737:chemistry; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D056148:Chromatography, Reverse-Phase; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D059748:Proteolysis
chemical_list: D000475:Alkenes; D023181:Antimicrobial Cationic Peptides; D001514:Bee Venoms; C545067:lasioglossin III; C534036:melectin