title: Structure-activity study of macropin, a novel antimicrobial peptide from the venom of solitary bee Macropis fulvipes (Hymenoptera: Melittidae).
abstract: A novel antimicrobial peptide, designated macropin (MAC-1) with sequence Gly-Phe-Gly-Met-Ala-Leu-Lys-Leu-Leu-Lys-Lys-Val-Leu-NH2 , was isolated from the venom of the solitary bee Macropis fulvipes. MAC-1 exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria, antifungal activity, and moderate hemolytic activity against human red blood cells. A series of macropin analogs were prepared to further evaluate the effect of structural alterations on antimicrobial and hemolytic activities and stability in human serum. The antimicrobial activities of several analogs against pathogenic Pseudomonas aeruginosa were significantly increased while their toxicity against human red blood cells was decreased. The activity enhancement is related to the introduction of either l- or d-lysine in selected positions. Furthermore, all-d analog and analogs with d-amino acid residues introduced at the N-terminal part of the peptide chain exhibited better serum stability than did natural macropin. Data obtained by CD spectroscopy suggest a propensity of the peptide to adopt an amphipathic α-helical secondary structure in the presence of trifluoroethanol or membrane-mimicking sodium dodecyl sulfate. In addition, the study elucidates the structure-activity relationship for the effect of d-amino acid substitutions in MAC-1 using NMR spectroscopy.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610, Prague 6, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Monincová
authors.forename: Václav
authors.initials: V
authors.lastname: Veverka
authors.forename: Jiřina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Vladimír
authors.initials: V
authors.lastname: Fučík
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: Ceřovský
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001514:Bee Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001516:Bees / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D001514:Bee Venoms; C000593910:macropin, Macropis fulvipes
keywords: CD spectroscopy; NMR spectroscopy; analog; antimicrobial peptide; wild bee venom