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Short host-defence peptides from frog skin
No full textGene-encoded antimicrobial peptides (AMPs) are key components of the innate immune response of all pluricellular organisms, providing them with the first-line defence against pathogens [1-4]. Amphibian skin secretions represent one of the richest natural sources for such molecules, which are synthesized and stored within granules of holocrine-type serous glands and released upon stimulation [5-7].We are studying two major groups, temporins and bombinins H. Temporins constitute a large family of AMPs (more than 40 members) isolated from the skin of the genus Rana, and are among the smallest amphipathic a-helical peptides (10-14 residues) found in nature to date, and with the lowest number of positively charged amino acids [8,9]. Interestingly, some temporins (A, B and L) do possess attractive and unique properties that make them promising candidates for the future design of anti-infective agents with new modes of action, urgently needed due to the increasing resistance of microorganisms to the available drugs. These properties include: (i) a fast membranolytic effect against a large spectrum of pathogens (bacteria, fungi and protozoa of Leishmania genus including both the insect and the mammalian stages of the parasite) [10,11]; (ii) preservation of biological activity in serum and in physiological salt concentration [11]; (iii) chemotactive activities on human phagocytes; (iv) synergistic action when combined with conventional antibiotics [12]; (v) in vivo efficacy in preventing prosthetic graft infections and lethality in rat models of septic shock. The second interesting family of AMPs refers to bombinins H, isolated from amphibia of Bombina genus [13] and containing isomers with a single D-amino acid which results from a post-traslational modification. By studying these peptides [14],we have demonstrated the importance of a single L- to D epimerization as a new approach developed by nature to modulate not only the bio-availability (e.g. higher solubility) and biostability (i.e. protection from proteolytic degradation) of these molecules, but also their biophysical properties (peptide structure and organization within membranes) and antimicrobial activities [15].
REFERENCES
[1] Boman H.G. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 1995; 13:61-92.
[2] Kimbrell D.A. and Beutler B. The evolution and genetics of innate immunity. Nat. Rev. Genet. 2001; 2:256-267.
[3] Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 2003; 3:710-720.
[4] Selsted M.E. and Ouellette A.J. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 2005; 6:551-557.
[5] Barra, D., and Simmaco, M. Amphibian skin: a promising resource for antimicrobial peptides, Trends Biotechnol. 1995; 13: 205-209.
[6] Bevins, C. L., and Zasloff, M. Peptides from frog skin, Annu. Rev. Biochem. 1990; 59:395-414.
[7] Mangoni, M. L., Miele, R., Renda, T. G., Barra, D., and Simmaco, M. The synthesis of antimicrobial peptides in the skin of Rana esculenta is stimulated by microorganisms, FASEB J. 2001; 15:1431-1432.
[8] Simmaco M., Mignogna G., Canofeni S., Miele R., Mangoni M.L., Barra D. Temporins, antimicrobial peptides from the European red frog Rana temporaria. Eur. J. Biochem. 1996; 242:788-792.
[9] Conlon J.M., Kolodziejek J. and Nowotny N. Antimicrobial peptides from ranid frogs: taxonomic and phylogenetic markers and a potential source of new therapeutic agents. Biochim. Biophys. Acta 2004;1696: 1-14.
[10] Mangoni M.L., Papo N., Barra D., Simmaco M., Bozzi A., Di Giulio A., Rinaldi AC. Effects of the antimicrobial peptide temporin L on cell morphology, membrane permeability and viability of Escherichia coli. Biochem. J. 2004; 380:859-865.
[11] Mangoni, M. L., Saugar, J. M., Dellisanti, M., Barra, D., Simmaco, M., Rivas, L. Temporins, small antimicrobial peptides with leishmanicidal activity, J. Biol. Chem. 2005; 280:984-990.
[12] Mangoni M.L., Rinaldi A.C., Di Giulio A., Mignogna G., Bozzi A., Barra D. Simmaco M. Structure-function relationships of temporins, small antimicrobial peptides from amphibian skin. Eur. J. Biochem. 2000; 267: 1447-1454.
[13] Mignogna, G., Simmaco, M., Kreil, G., Barra, D. Antibacterial and haemolytic peptides containing D-alloisoleucine from the skin of Bombina variegata, EMBO J. 1993; 12: 4829-4832.
[14] Mangoni, M. L., Grovale, N., Giorgi, A., Mignogna, G., Simmaco, M., Barra, D. Structure-function relationships in bombinins H, antimicrobial peptides from Bombina skin secretions, Peptides 2000; 21: 1673-1679.
[15] Mangoni M.L., Papo N., Saugar J.M., Barra D., Shai Y., Simmaco M., Rivas R. Biochemistry. 2006; in pres
ANTIMICROBIAL PEPTIDES FROM AMPHIBIAN SKIN: WHAT DO THEY TELL US?
No full textAmphibian skin secretions contain many biologically active compounds, such as biogenic
amines, complex alkaloids, or peptides. Within the latter class of molecules, a large number
of peptide antibiotics has been isolated and characterized from different amphibian species.
Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first
line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell
membrane. These gene-encoded molecules are synthesized as inactive precursors and in several
cases their proparts were shown to have highly conserved structures. It has also been demonstrated
that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional
control machinery NF-kB/IkBa. In amphibia of Rana and Bombina genera, inhibition of transcription
of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment,
which causes an increase of IkBa synthesis. Moreover, determination of the structure of a number
of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter
regions contain recognition sites for nuclear factors
Pianta transgenica con aumentata resistenza a organismi fitopatogeni e metodo per la sua preparazione.
No full textAMPHIBIAN SKIN: A PROMISING RESOURCE FOR ANTIMICROBIAL PEPTIDES
No full textAmphibian skin is a rich source of biologically active compounds that are assumed to have diverse physiological and defence functions. In addition to the range of pharmacologically active peptides present, some of which have mammalian homologues, skin secretions contain a broad spectrum of antimicrobial peptides. As yet, such peptides from only a few species have been studied, and screening of other species is expected to yield further new antimicrobial activities. Natural antimicrobial peptides isolated from amphibian skin could provide lead structures for either the chemical, or rDNA synthesis of novel antimicrobials
Bombinins, antimicrobial peptides from Bombina species
No full textThe skin secretions of Bombina species contain peptides and small proteins with interesting biological properties. These include bombesin, thyrotropin releasing hormone, BSTI and Bv8. In this review, the biosynthesis and antimicrobial activity of two groups of peptides, bombinins and bombinins H, are described. To date, these have only been found in Bombina skin. They are derived from common precursors containing one or two bombinin copies at the amino and a single bombinin H at the carboxyl end. Bombinins are active against Gram-positive and Gram-negative bacteria and fungi but virtually inactive in haemolysis assays. Conversely, bombinins H have lower bactericidal activities but lyse erythrocytes. In the skin secretions, bombinins H are present in two sizes with either 20 or 17 amino acids. Moreover, they occur as epimers with either an L- or a D-amino acid at position 2. An enzyme catalyzing this inversion of chirality of an amino acid in peptide linkage has been isolated from Bombina skin secretions. in different tests, also with different stages of the life cycle of Leishmania parasites, the D-forms were found to be more active. Biophysical studies have yielded some insight into the different behaviours of the epimers in model membranes. (C) 2009 Elsevier B.V. All rights reserved
Partial amino-acid sequence and cysteine reactivities of cytosolic aspartate aminotrasferase from horse heart
Full text linkANTIMICROBIAL PEPTIDES FROM SKIN SECRETIONS OF RANA ESCULENTA. MOLECULAR CLONING OF cDNAs ENCODING ESCULENTIN AND BREVININS AND ISOLATION OF NEW ACTIVE PEPTIDES
No full textThree cytolytic peptides, termed brevinin-1E, brevinin-2E, and esculentin, were isolated from skin secretions of the European frog Rana esculenta (Simmaco, M., Mignogna, G., Barra, D., and Bossa, F. (1993) FEBS Lett. 324, 159-161). Nucleotide sequence analysis of cDNAs coding for the corresponding precursors revealed that in all of them a single copy of the sequence of the mature peptide is present preceded by a dibasic cleavage site and followed by a stop codon. The signal peptides of these precursors show a clear homology to the corresponding region of the precursor of dermorphin, a neuropeptide occurring in the skin of amphibians of the subfamily Phyllomedusinae. Ten new peptides, ranging in size from 24 to 46 residues, all possessing an intramolecular disulfide bridge located at the carboxyl-terminal end, were isolated from skin secretions of R. esculenta. These peptides can be grouped into four subfamilies on the basis of their distinctive structural and/or functional properties. All of these new peptides have antimicrobial and/or hemolytic activities typical for the respective subfamily. In addition, we demonstrate that esculentin-1 also inhibits the growth of Pseudomonas aeruginosa, Candida albicans, and Saccharomyces cerevisiae
THERMODYNAMIC ANALYSIS OF THE BINDING OF THE POLYGLUTAMATE CHAIN OF 5-FORMYLTETRAHYDROPTEROYLPOLYGLUTAMATES TO SERINE HYDROXYMETHYLTRANSFERASE
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