583 research outputs found
Defensins
No full textThe term defensin relates to a set of host defense peptides (HDPs)in vertebrates, invertebrates, plants, and
molds that display structural similarities based on a cystine stabilized antiparallel bet-sheetcore, with an
alpha-helical stretch also present in some membrers, Defensins of different origins exhibit structural and
functional similarities, with phylogenetic relationships between invertebrate and plant defensins, and
between different types of vertebrate defensisn, and a possible common bacterl ancestor. Most defensins
demonstrate a direct anbtimicrobial action in vitro with varyiing activity spectra. This requires
interaction with components of the microbial cell wall, and often involves membrane permeabilization,
although the mode of action differes markedly for defensins both within and from different families.
Defensins also play important regulatory roles in the immune system of animals and plants,acting as a bridge
between innate and adaptive immunity in vertebrates. Roles outside host defense have also been reported
PEG-IFN alpha 2b and alpha 2a: quali differenze nella loro farmacocinetica e farmacodinamica sono clinicamente rilevanti?
No full textPOSSIBILI CORRELAZIONI TRA L’ATTIVITA’ DELLA B -GLUCURONIDASI SALIVARE E IL CICLO MESTRUALE.
No full textIdentification of antimicrobial peptides from teleosts and anurans in expressed sequence tag databases using conserved signal sequences.
No full textThe problem of multidrug resistance requires the efficient and accurate identification of new classes of antimicrobial agents. Endogenous antimicrobial peptides produced by most organisms are a promising source of such molecules. We have exploited the high conservation of signal sequences in teleost and anuran antimicrobial peptides to search cDNA (expressed sequence tag) databases for likely candidates. Subject sequences were then analysed for the presence of potential antimicrobial peptides based on physicochemical properties (amphipathic helical structure, cationicity) and use of the D-descriptor model to predict the therapeutic index (relation between the minimum inhibitory concentration and the concentration giving 50% haemolysis). This analysis also suggested mutations to probe the role of the primary structure in determining potency and selectivity. Selected sequences were chemically synthesized and the antimicrobial activity of the peptides was confirmed. In particular, a short (21-residue) sequence, likely of sticklefish origin, showed potent activity and it was possible to tune the spectrum of action and/or selectivity by combining three directed mutations. Membrane permeabilization studies on both bacterial and host cells indicate that the mode of action was prevalently membranolytic. This method opens up the possibility for more effective searching of the vast and continuously growing expressed sequence tag databases for novel antimicrobial peptides, which are likely abundant, and the efficient identification of the most promising candidates among them
Native oligomerization determines the mode of action and biological activities of human cathelicidin LL-37
No full textLL-37 is a multifunctional component of innate immunity, with a membrane-directed antimicrobial activity and receptor-mediated pleiotropic effects on host cells. Sequence variations in its primate orthologues suggest two types of functional features have evolved; human LL-37-like peptides form amphipathic helical structures and self-assemble under physiological conditions, while rhesus RL-37-like ones only adopt this structure in the presence of bacterial membranes. The first type of peptide has a lower and more medium-sensitive antimicrobial activity than the second, but an increased capacity to stimulate host cells. Oligomerization strongly affects the mode of interaction with biological membranes and consequently both cytotoxicity and receptor-mediated activities. In this work we explored the effects of LL-37 self-association by using obligate, disulfide-linked dimers with either parallel or anti-parallel orientations. These had an increased propensity to form stacked helices in bulk-solution and when in contact with either anionic or neutral model membranes. The antimicrobial activity against Gram-positive or Gram-negative bacteria, as well as the cytotoxic effects on host cells, strongly depended on the type of dimerization. To investigate the extent of native oligomerization we replaced Phe5 with the photoactive residue p-Benzoyl-L-Phenylalanine (Bpa), which on UV irradiation enabled covalent cross-linking and allowed us to assess the extent of oligomerization in both physiological solution and in model membrane
Porte Logiche Reversibili nella Computazione Quantistica: implementazione del compilatore quantistico QBITER
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