title: Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and analogs:structural and disulfide bridge requirements for activity.
abstract: Structure and biological activities of synthetic peptides corresponding to bovine neutrophil beta-defensin BNBD-12, GPLSC(1)GRNGGVC(2)IPIRC(3) PVPMRQIGTC(4) FGRPVKC(5) C(6)RSW with disulfide connectivities C(1)-C(5), C(2)-C(4) and C(3)-C(6) and its variants with one, two and three disulfide bridges have been investigated. Selective protection of cysteine thiols was necessary in the four and six cysteine containing peptides for the formation of disulfide connectivities as observed in BNBD-12. Circular dichroism (CD) spectra indicate that in aqueous medium, only a small fraction of molecules populate turn-like conformations. In the presence of micelles and lipid vesicles, the single, two and three disulfide containing peptides adopt beta-hairpin or beta-sheet structures. Antibacterial activity was observed for all the peptides, irrespective of the number of disulfide bridges or how they were connected. Our results suggest that a rigid beta-sheet structure or the presence of three disulfide bridges does not appear to be stringent requirements for antibacterial activity in beta-defensins.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, 500 007, Hyderabad, India.
authors.forename: M
authors.initials: M
authors.lastname: Mandal
authors.forename: M V
authors.initials: MV
authors.lastname: Jagannadham
authors.forename: R
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000187:drug effects*; D023083:beta-Defensins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004220:Disulfides; D023083:beta-Defensins; C406410:bovine neutrophil beta-defensin 12