Total synthesis in solution and conformational analysis of the peptaibol cervinin and selected analogues

The total synthesis in solution and chemical characterization of the antibacterial undecamer peptaibol cervinin, its C-terminal (Lol-Ac) derivative, also naturally occurring, and three selected analogues modified at the N- and/or C-terminus(i) to improve the affinity to the membrane environment, are described. A solution conformational analysis in different media, performed by the combined use of FT-IR, CD, and 2D-NMR techniques, clearly shows a significant 310-like helicity for these Aib-Pro rich peptides. The hydrophilicity/lipophilicity characteristics of the final compounds significantly influence their membrane-modifying properties.