Peptaibolin: synthesis, 3D-structure, and membrane modifying properties of the natural antibiotic and selected analogues

We synthesized by solution methods and fully characterized the naturally occurring, tetrapeptide antibiotic peptaibolin and selected analogues with replacements at the N- and C-terminal groups and the C-alpha-tetrasubstituted alpha -amino acids. The preferred conformation of all of the peptides was assessed in solution by using FT-IR absorption and H-1 NMR techniques. Results of the X-ray diffraction analyses of peptaibolin itself and three analogues are also presented. Permeability measurements of such multiple turn forming, very short peptides indicate that peptaibolin is devoid of membrane activity because a lipoyl N-terminal blocking group is an essential requisite. (C) 2001 Elsevier Science Ltd. All rights reserved.