Premium
Conformational Analysis of TOAC‐Labelled Alamethicin F50/5 Analogues
Author(s) -
Peggion Cristina,
Jost Micha,
De Borggraeve Wim M.,
Crisma Marco,
Formaggio Fernando,
Toniolo Claudio
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790108
Subject(s) - alamethicin , chemistry , stereochemistry , amide , crystallography , membrane , biochemistry , lipid bilayer
In the preceding paper in this issue, we reported the total syntheses in solution of a set of four TOAC‐containing analogues of the [ L ‐Glu(OMe) 7,18,19 ] F50/5 component of alamethicin, the prototype of peptaibol antibiotics forming channels in the biological membranes. In this article, we have expanded this work to the examination of their preferred conformation in solution by use of a combination of CD, FT‐IR absorption, and NMR spectroscopies. The results are strongly in favor of the view that replacement of the Aib residues at positions 1, 8, and 16 with TOAC (both are members of the helicogenic sub‐class of C α ‐tetrasubstituted α ‐amino acids) does not significantly affect the overwhelmingly populated α ‐helical 3D structure of alamethicin. The X‐ray diffraction crystal structure of the N α ‐protected, C‐terminal, hexapeptide amide segment Z‐ L ‐Pro‐ L ‐Val‐(Aib) 2 ‐[ L ‐Glu(OMe)] 2 ‐Fol lends further support to our conformational conclusions.