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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Increasing Amphiphilicity in Peptaibiotics: Gly to LysReplacements in Trichogin GA IVMarta De Zotti 1 , Barbara Biondi 1 , Cristina Peggion 1 ,Fernando Formaggio 1 , Yoonkyung Park 2,3 , Kyung-Soo Hahm 3,4 ,and Claudio Toniolo 11 ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, Padova, 35131,Italy; 2 Department of Biotechnology, Chosun University, Gwangju, 501-759, Korea;3 Department of Biomaterials, Chosun University, Gwangju, 501-759, Korea; 4 Departmentof Cellular and Molecular Medicine, Chosun University, Gwangju, 501-759, KoreaIntroductionTrichogin GA IV, isolated from the fungus Trichoderma longibrachiatum [1], is theprototype of lipopeptaibols [2], the sub-class of short-length peptaibiotics exhibitingmembrane-modifying properties. The primary structure of the 10-amino acid peptidetrichogin GA IV is as follows:1-Oct-Aib-Gly-Leu-Aib-Gly-Gly-Leu-Aib-Gly-Ile-Lol(1-Oct, 1-octanoyl; Aib, -aminoisobutyric acid; Lol, leucinol). In previous papers we haveshown, using a variety of physico-chemical techniques including X-ray diffraction, that thispeptaibol is predominantly folded in a mixed 3 10 -/ - helical conformation with a clear,albeit modest, amphiphilic character [3].Results and DiscussionIn this work we synthesized by the solid-phase methodology, purified, and fullycharacterized (Figure 1) a set of trichogin GA IV analogues in which the four Gly residuesat positions 2, 5, 6, 9, lying on the poorly hydrophilic face of the helical structure, aresubstituted by one (position 2 or 9), two (positions 5 and 6), three (positions 2, 5, and 9), orfour (positions 2, 5, 6, and 9) Lys residues. The analogue with the triple Lys replacementwas additionally modified by the incorporation of a helix-inducing Aib residue atposition 6.ABC[Aib 6 ,Lys 2,5,9 ]-trichogin[Lys 5,6 ]-trichogin[Lys 2,5,6,9 ]-trichoginB13.9 minA15.2 minAbsorbanceC9.5 min10 15 20time (min)Fig. 1. RP-HPLC chromatograms obtained for the trichogin analogues containing two(B), three (A) and four (C) Lys residues. Column: Vydac C 18 ; gradient: 50-90% B in25min; eluants: A: H 2 O+0.1 %TFA, B: CH 3 CN/H 2 O 9:1+0.1 % TFA.390