Sella, Valentina (2011) Sintesi e caratterizzazione di coniugati di peptidi antimicrobici con porfirine cationiche e valutazione dell'attivit√† fototossica. [Laurea specialistica biennale]
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The worldwide rise of antibiotic resistance stimulates the search of new strategies for killing bacteria, whose mechanisms of action are different from those of antibiotics. Two promising strategies are the use of antimicrobial peptides, that represent a primary line of defence innate against the microbial aggressions, and the photodynamic therapy (PDT). PDT utilizes a visible light absorbing molecule, called photosensitizer (PS), that in the presence of oxygen generates cytotoxic reactive species that kill bacterial cells previously loaded with the PS. Our attention is focused on the synthesis, characterization and defence role of conjugates between antimicrobial peptides and porphyrin cationic, because they can have an effect on bacteria specific target cellular. Apidaecin 1b or Magainin II was conjugated to a photoactive porphyrin, the 5-(4-carboxyphenyl)-10,15,20-tris-(4 pyridyl)-porphyrin (TPPYCOOH), to obtain a new and broad-spectrum antimicrobial agent. These conjugates are purified by HPLC and characterized by spectroscopy UV-Vis and circular dichroism. Their cytotoxic activity have been investigated on Gram negatives and Gram positives bacteria: the results of preliminary investigations suggest that coniugates antimicrobial peptides- porphiryns could represent an alternative to antibiotics in the therapy of infectious diseases, therefore the current research suggests it should optimize the balance between the hydrofilic and hydrofobic components of conjugates. Thus, it was demonstrated that the conjugation of an antimicrobial peptide with a photoactive molecule can lead to the formation of antimicrobial agents very effective and displaying a broader activity in comparison to the single components.
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