bmap-28 and Hemolysis

bmap-28 has been researched along with Hemolysis* in 2 studies

Other Studies

2 other study(ies) available for bmap-28 and Hemolysis

ArticleYear
Stability, toxicity, and biological activity of host defense peptide BMAP28 and its inversed and retro-inversed isomers.
    Biopolymers, 2011, Volume: 96, Issue:1

    Host defense peptides (HDPs) contribute to immune defense through direct antimicrobial activity as well as modulation of host immune responses. While the antimicrobial activity of HDPs has been successfully exploited as topical antibiotics, their use as systemic immunomodulatory antimicrobials has been limited by their toxicity and biological instability. Peptide modification strategies to address these characteristics, while maintaining biological activity, are likely essential to capture the full therapeutic potential of HDPs. Here we investigate the stability, toxicity, and biological activity of the L, inversed (D), and retro-inversed (RI) isomers of BMAP28. The D and RI isomers both form symmetrically related structures to L BMAP28 and resist proteolytic degradation. With respect to toxicity, the considerable hemolytic activity of L BMAP28 is approximately halved with the D isomer and eliminated with RI BMAP28. Furthermore, while D BMAP28 maintains the same cytotoxicity profile against epithelial cells and monocytes as the natural peptide, RI BMAP28 is markedly less toxic against these cell types. As prophylactic antimicrobials, all three isomers significantly reduced bacterial loads [99.99% bacterial clearance by each peptide at the highest dose (20 mg kg(-1) )], when administered 18 h prior to challenge in a mouse model of peritoneal infection. This protection appears to be mediated through neutrophil recruitment and activation of macrophages for bacterial clearance. Collectively, the increased stability and retained biological activity of D and RI BMAP28 make these isomers attractive as antimicrobial therapeutics. In particular, the protection conferred by RI BMAP28, combined with its reduced toxicities, make it a strong candidate for further consideration.

    Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteria; Bacterial Infections; Cattle; Cell Survival; Cells, Cultured; Circular Dichroism; Dose-Response Relationship, Drug; Female; Hemolysis; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Sequence Data; Monocytes; Peptide Hydrolases; Phagocytes; Phagocytosis; Protein Isoforms; Protein Stability; Proteins

2011
Structure-function study of cathelicidin-derived bovine antimicrobial peptide BMAP-28: design of its cell-selective analogs by amino acid substitutions in the heptad repeat sequences.
    Biochimica et biophysica acta, 2009, Volume: 1788, Issue:11

    Although BMAP-28 is a potent cathelicidin-derived bovine antimicrobial peptide, its cytotoxic activity against the human and other mammalian cells is of concern for converting it into a novel antimicrobial drug. We have identified a short leucine and isoleucine zipper sequences at the N- and C-terminals of BMAP-28, respectively. To understand the possible role of these structural elements in BMAP-28, a number of alanine-substituted analogs were designed, synthesized and characterized along with the wild-type peptide. The substitution of amino acids at single or multiple 'a' position(s) of these structural motifs by alanine showed significant effects on the cytotoxic activity of the molecule on the human red blood cells (hRBCs) and 3T3 cells without showing much effects on their MIC values against the selected bacteria. BMAP-28 and all its analogs depolarized the Escherichia coli cells with almost equal efficacy. In contrast, the alanine-substituted analogs of BMAP-28 depolarized hRBCs much less efficiently than the parent molecule. Results further showed that BMAP-28 assembled appreciably onto the live E. coli and hRBC. However, the selected less toxic analogs of BMAP-28 although assembled as good as the parent molecule onto the live E. coli cells, their assembly onto the live mammalian hRBCs was much weaker as compared to that of the wild-type molecule. Looking at the remarkable similarity with the data presented in our previous work on melittin, it appears that probably the heptad repeat sequence possesses a general role in maintaining the cytotoxicity of the antimicrobial peptides against the mammalian cells and assembly therein.

    Topics: 3T3 Cells; Amino Acid Sequence; Amino Acid Substitution; Animals; Anti-Bacterial Agents; Cattle; Cell Membrane; Erythrocytes; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Hemolysis; Humans; Mice; Microbial Sensitivity Tests; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; Proteins; Repetitive Sequences, Amino Acid; Sequence Homology, Amino Acid; Structure-Activity Relationship

2009