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

We synthesized by solution methods and fully characterized the naturally oc curring, tetrapeptide antibiotic peptaibolin and selected analogues with re placements 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. Resu lts of the X-ray diffraction analyses of peptaibolin itself and three analo gues are also presented. Permeability measurements of such multiple turn fo rming, very short peptides indicate that peptaibolin is devoid of membrane activity because a lipoyl N-terminal blocking group is an essential requisi te. (C) 2001 Elsevier Science Ltd. All rights reserved.