Sintesi, caratterizzazione e studi conformazionali di analoghi dell'antibiotico naturale tricogina GA IV, contenenti l'amminoacido pNO2Phe

All the peptides have been prepared by solid phase peptide synthesis with high yields and good purity. All the peptides have been The aim of the present thesis is the comprehension of the antibiotic activity of the peptaibol trichogin GA IV. Three analogues of the naturally occurring trichogin GA IV containing the para-nitrophenylalanine residue at different positions in the sequence have been prepared. The synthesized peptides are as follows: • n-octanoyl-Aib-Gly-L-pNO2-Phe-Aib-Gly-Gly-L-Leu-Aib-Gly-L-Ile-L-Lol (3) • n-octanoyl-Aib-Gly-L-Leu-Aib-Gly-Gly-L-pNO2-Phe-Aib-Gly-L-Ile-L-Lol (7) • n-octanoyl-Aib-Gly-L-Leu-Aib-Gly-Gly-L-Leu-Aib-Gly-L-pNO2-Phe-L-Lol (10) Moreover, the synthesis of a new analogue of trichogin, with enhanced selectivity versus bacterial membranes, has been planned. Its sequence is the following: n-ottanoil-Aib-Gly-L-Leu-Aib-Gly-Gly-L-Leu-Aib-Gly-L-Ile-L-Leu-O-NH-R. R=DMP fully characterized and their conformation has been assessed by 1H NMR, FT-IR absorption and circular dichroism. All the compounds adopt stable helical structures. The pNO2-Phe residue has been investigated by FT-IR in solutions and ATR-FTIR , to understand the orientation of the helices once in contact with the different environment (e.g. solvent and phospholipidic bilayers). Studies of carboxyfluorescein leakage from artificial liposomes have been conducted, to investigate the ability of peptides 3, 7 and 10 to interact with model membranes. In vitro test have been made on all the three analogues containing the pNO2-Phe residue.