Trichogin: a paradigm for lipopeptaibols

Lipopeptaibols are members of a novel family of naturally occurring, short peptides with antimicrobial activity, characterized by a lipophilic acyl chain at the N ‐terminus, a high content of turn/helix inducing α‐aminoisobutyric acid and a 1,2‐amino alcohol at the C ‐terminus. Using solution methods, the prototypical lipopeptaibol trichogin GA IV and a large series of appropriately designed analogues were synthesized, which allow: (i) determination of the minimal lipid chain and peptide main‐chain lengths for the onset of membrane activity, and (ii) exploitation of a number of physico‐chemical techniques aimed at assessing the trichogin preferred conformation under a variety of conditions and at investigating its mechanism of interaction with the phospholipid membranes. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.