Fabris , Cecilia (2013) Progettazione, sintesi e studio di nuovi peptidi antimicrobici a sequenza corta Design, synthesis and study of new ultrashort antimicrobial peptides. [Magistrali biennali]
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Drug resistance of microbes against antifungal drugs is a recent and concerning issue. To combat this challenge, new antimicrobial agents have been developed to stem the rising number of infections. Amongst these novel approaches, an innovative and promising class of therapeutic agents are peptidic antimicrobial drugs. New ultrashort polycationic peptides and lipopeptides with antimicrobial activity were synthesized. Different sequences were designed using hydrophobic and basic amino acids, a variable lipophilic group attached at the N-terminal moiety and an ethylenediamine linker attached at the C-terminal moiety. Furthermore sequences were synthesized using both L- and D-amino acids, in order to increase the selectivity against bacterial cells and reduce adverse toxic effects on mammalian cells. Other peptides were synthesized using Aib residue, to promote the formation of helical secondary structures. The synthesized peptides were studied by means of 1D- and 2D- 1H NMR techniques, HPLC, mass spectrometry, IR and CD. Activity tests were done using small unilamellar vesicles that mimic bacterial and mammalian cell membranes. Peptides were functionalized with a C-terminal ethylenediamine linker, that can be bound covalently to cotton fibers. In this way the production of antimicrobial textiles for immunocompromised patients and health workers is achievable. The simple composition and the short peptide chain length make these peptides very interesting as economically viable drugs. Synthesis and characterization of the peptides was carried out in the laboratory of bioorganic chemistry at Università degli studi di Padova, under the supervision of Dr. Cristina Peggion. Regarding the synthesis of the Cα-tetrasubstitued amino acid bis-lysine, the job took place in the laboratory of organic chemistry at Katholieke Universiteit Leuven, under the supervision of Prof. Wim De Borggraeve.
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