antimicrobial-peptide-ib-367 and protegrin-1

antimicrobial-peptide-ib-367 has been researched along with protegrin-1* in 3 studies

Reviews

1 review(s) available for antimicrobial-peptide-ib-367 and protegrin-1

ArticleYear
The role of defensins in lung biology and therapy.
    American journal of respiratory medicine : drugs, devices, and other interventions, 2002, Volume: 1, Issue:4

    Innate host defence, involving both cellular and humoral mediators, is a prominent function of the human airways. Cellular mediators of innate immunity include dendritic cells, natural killer cells, cytotoxic T cells, macrophages and neutrophils, while humoral mediators of innate immunity consist of components of the epithelial lining fluid (ELF) covering the airways. Microbicidal substances in the ELF can selectively disrupt bacterial cell walls and membranes, sequester microbial nutrients or act as decoys for microbial attachment. Antimicrobial components of airway secretions include lysozymes, lactoferrin, secretory leukoprotease inhibitor, defensins and cathelicidins. Defensins are the most widely studied family of antimicrobial peptides present in airway fluid. Humans produce at least 10 different defensin molecules, six alpha-defensins and four beta-defensins similar in structure and function. Direct evidence that defensins have central roles in host defense has only recently become available. Some defensins and defensin-like molecules could serve as templates for the development of pulmonary pharmaceuticals. As potential therapeutics, they possess several desirable properties, including the ability to kill a broad spectrum of micro-organisms while permitting little development of microbial resistance. Many peptides can also neutralize effects of lipopolysaccharide on macrophages and other host defense cells and decrease the release of proinflammatory cytokines thereby giving protection against septic shock. Protegrin-1 is a minidefensin isolated from pig leukocytes and has proved to be an attractive template for large-scale development of antibacterials. One such protegrin analog, iseganan is in phase III clinical trials for the treatment of oral mucositis secondary to systemic chemotherapy. Other prospective uses of iseganan include control of respiratory pathogens in patients with cystic fibrosis and reduction of oral bacteria to prevent ventilator-associated pneumonia. However, in order to advance the production and clinical testing of peptide-based therapeutics, technical hurdles of synthesizing large quantities of complexly folded peptides must be first overcome. Strategies to develop potent peptide-based microbicides are promising in the struggle against increasingly resistant pathogens.

    Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Clinical Trials as Topic; Defensins; Disease Models, Animal; Drugs, Investigational; Humans; Lung; Lung Diseases; Molecular Sequence Data; Peptides; Proteins

2002

Other Studies

2 other study(ies) available for antimicrobial-peptide-ib-367 and protegrin-1

ArticleYear
Antimicrobial and conformational studies of the active and inactive analogues of the protegrin-1 peptide.
    The FEBS journal, 2010, Volume: 277, Issue:4

    The natural antimicrobial cationic peptide protegrin-1 displays a broad spectrum of antimicrobial activity and rapidly kills pathogens by interacting with their cell membrane. We investigated the structure-activity relationships of three protegrin-1 analogues: IB-367 (RGGLCYCRGRFCVCVGR-NH(2)), BM-1 (RGLCYCRGRFCVCVG-NH(2)) and BM-2 (RGLCYRPRFVCVG-NH(2)). Our antimicrobial and antifungal activity studies of these peptides showed that BM-1 was much more active than IB-367 against Gram-positive bacteria and fungi, whereas BM-2 was inactive. The BM-1 peptide showed fourfold reduced haemolysis relative to IB-367, an additional advantage of this peptide. In addition, BM-1 was about 15% cheaper than IB-367 to synthesize. The absence of two cysteine residues in the BM-2 sequence could be the main reason for its unstable conformation and antimicrobial inactivity. The solution structures of these peptides were determined in dimethyl sulphoxide using two-dimensional NMR and restrained molecular dynamics calculations. IB-367 and BM-1 formed short, antiparallel, beta-hairpin structures connected by a type II' beta-turn. The shorter, inactive BM-2 analogue exhibited major and minor conformations (predominantly unordered) in the NMR spectra and was much more flexible.

    Topics: Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteria; Fungi; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Models, Molecular; Oligopeptides; Protein Structure, Tertiary; Structure-Activity Relationship

2010
IB-367, a protegrin peptide with in vitro and in vivo activities against the microflora associated with oral mucositis.
    Antimicrobial agents and chemotherapy, 2000, Volume: 44, Issue:7

    Although the microflora associated with oral mucositis initiated by cytotoxic therapy is not well characterized, several studies suggest that reduction of the microbial load in the oral cavity has some clinical benefit. The MICs of IB-367, a synthetic protegrin analog, ranged from 0.13 to 64 microgram/ml for gram-positive bacteria (Streptococcus mitis, Streptococcus sanguis, Streptococcus salivarius, and Staphylococcus aureus) and from 0.06 to 8 microgram/ml for gram-negative species (Klebsiella, Escherichia, and Pseudomonas). IB-367 exhibited rapid, microbicidal activity against both log- and stationary-phase cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. At concentrations near the MICs for these two organisms (4 and 2 microgram/ml, respectively), IB-367 reduced viability by more than 3 logs in less than 16 min. Similarly, IB-367 effected a 4-log reduction of the endogenous microflora in pooled human saliva within 2 min at 250 microgram/ml, a concentration readily attained by local delivery. After nine serial transfers at 0.5x the MIC, the MIC of IB-367 for MRSA and P. aeruginosa increased only two to four times. In a phase I clinical study with healthy volunteers, IB-367 was well tolerated, with no detectable systemic absorption. One hour after treatment with 9 mg of IB-367, the prevalence of gram-negative bacteria and yeast was reduced, and the density of the predominant gram-positive oral flora was decreased 1,000 times. IB-367's properties (speed of killing, breadth of spectrum, and lack of resistance) make the compound a strong candidate for the prophylaxis of oral mucositis. Phase II clinical trials with IB-367 are under way for this indication in immunocompromised subjects.

    Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Drug Resistance, Microbial; Escherichia; Humans; Klebsiella; Microbial Sensitivity Tests; Mouth Diseases; Mouth Mucosa; Peptides; Proteins; Saliva; Streptococcus

2000