Infrared Spectroscopy as a Probe for the Development of Secondary Structure in the Amino-Terminal Segment of Alamethicin

摘要

Peptides containing lpha-aminoisobutyryl (Aib) residues have been shown to adopt well-defined structures in solution, by 1H NMR methods [1]. Theoretical studies suggest that the presence of geminal methyl substituents at $C^{lpha}$ imposes severe restrictions on the conformations accessible to Aib residues [2,3]. Single crystal X-ray diffraction studies of Z-Aib-Pro-NHMe[4], Z-Aib-Pro-Aib-Ala-OMe [5] and $Tosyl-{(Aib)}_5-OMe$ [6] have clearly established the tendency of Aib residues to adopt $3_{10}$ helical conformations and to initiate the formation of type III eta bends, stabilised by 4 ightarrow 1 intramolecular hydrogen bonds. Interest in the stereochemistry of Aib containing peptides, stems from the fact that alamethicin [7,8] and the related polypeptide ionophores antianioebin [9], emmerimicin [10], suzukacillin [11] and trichotoxin [12] contain high proportions of Aib residues. Here, we report the results of an infrared spectroscopic study of synthetic alamethicin fragments and demonstrate the development of a $3_{10}$ helical structure at the amino-terminus of the antibiotic.