tyrocidine has been researched along with Hemolysis* in 3 studies
3 other study(ies) available for tyrocidine and Hemolysis
Article | Year |
---|---|
Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.
The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized. Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Escherichia coli; Hemolysis; Humans; Models, Molecular; Staphylococcal Infections; Staphylococcus aureus; Tyrocidine | 2017 |
Inhibition of malaria parasite blood stages by tyrocidines, membrane-active cyclic peptide antibiotics from Bacillus brevis.
Tyrothricin, a complex mixture of antibiotic peptides from Bacillus brevis, was reported in 1944 to have antimalarial activity rivalling that of quinine in chickens infected with Plasmodium gallinaceum. We have isolated the major components of tyrothricin, cyclic decapeptides collectively known as the tyrocidines, and tested them against the human malaria parasite Plasmodium falciparum using standard in vitro assays. Although the tyrocidines differ from each other by conservative amino acid substitutions in only three positions, their observed 50% parasite inhibitory concentrations (IC(50)) spanned three orders of magnitude (0.58 to 360 nM). Activity correlated strictly with increased apparent hydrophobicity and reduced total side-chain surface area and the presence of ornithine and phenylalanine in key positions. In contrast, mammalian cell toxicity and haemolytic activities of the respective peptides were considerably less variable (2.6 to 28 microM). Gramicidin S, a structurally analogous antimicrobial peptide, was less active (IC(50)=1.3 microM) and selective than the tyrocidines. It exerted its parasite inhibition by rapid and selective lysis of infected erythrocytes as judged by fluorescence and light microscopy. The tyrocidines, however, did not cause an overt lysis of infected erythrocytes, but an inhibition of parasite development and life-cycle progression. Topics: Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Bacillus; Dose-Response Relationship, Drug; HeLa Cells; Hemolysis; Humans; Life Cycle Stages; Microscopy, Fluorescence; Plasmodium falciparum; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Toxicity Tests; Tyrocidine | 2007 |
Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic.
Using an alanine-scanning method, we have found that the antibacterial and hemolytic activities of the amphipathic cyclic decapeptide antibiotic tyrocidine A depend on different structural components. Single substitution of glutamine-6 of the natural product with a cationic amino acid results in a therapeutic index enhancement of up to 140-fold. Successful dissociation of the two intimately associated properties should enable discovery of novel analogues with both high bacterial selectivity and antibacterial potency to counter microbial resistance. Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacillus subtilis; Chromatography, High Pressure Liquid; Drug Resistance, Bacterial; Hemolysis; Humans; In Vitro Techniques; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Peptides, Cyclic; Protein Structure, Secondary; Spectrometry, Mass, Fast Atom Bombardment; Structure-Activity Relationship; Tyrocidine | 2003 |