Myotoxic phospholipases A2 isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells
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2008-10-01
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This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A2 (PLA2s) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing Mr ∼ 14,000 for the monomer and 28,000 Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA2s from snake venoms, MTX-I belonging to Asp49 PLA2 class, enzymatically active, and MTX-II to Lys49 PLA2s, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA2 and anticoagulant activities, corroborating the importance of residue His48 and Ca2+ ions for the enzymatic catalysis. Both PLA2s induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA2 proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer. © 2008 Elsevier Inc. All rights reserved.
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Bothrops brazili, Cytotoxicity, Microbicide, Myotoxins, Phospholipases A2, Snake venom, Synthetic peptides, dimer, edetic acid, histidine, lysine, monomer, myotoxin 1, myotoxin 2, phospholipase A2, sepharose, snake venom, synthetic peptide, unclassified drug, amino terminal sequence, animal experiment, animal model, anticoagulation, antimicrobial activity, Candida albicans, carboxy terminal sequence, catalysis, controlled study, cytotoxicity, edema, enzyme activity, Escherichia coli, human, human cell, Leishmania, male, mouse, nonhuman, priority journal, snake, T cell leukemia, Amino Acid Sequence, Animals, Bothrops, Cell Line, Tumor, Crotalid Venoms, Humans, Isoenzymes, Male, Mice, Microbial Sensitivity Tests, Molecular Sequence Data, Peptide Mapping, Peptides, Sequence Alignment, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Crotalus, Leishmania sp.
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Inglês
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Peptides, v. 29, n. 10, p. 1645-1656, 2008.
