title: Conformational analysis of TOAC-labelled alamethicin F50/5 analogues.
abstract: 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(alpha)-tetrasubstituted alpha-amino acids) does not significantly affect the overwhelmingly populated alpha-helical 3D structure of alamethicin. The X-ray diffraction crystal structure of the N(alpha)-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.
authors.affiliation: Institute of Biomolecular Chemistry, Padova Unit, CNR, Department of Chemistry, University of Padova, Padova.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.forename: Micha
authors.initials: M
authors.lastname: Jost
authors.forename: Wim M
authors.initials: WM
authors.lastname: De Borggraeve
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D003497:Cyclic N-Oxides / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D003497:Cyclic N-Oxides; D000408:Alamethicin; C037109:2,2,6,6-tetramethylpiperidine-N-oxide-4-amino-4-carboxylic acid