Note: Helix or No Helix of β-Peptides Containing β3hAla(αF) Residues?

A remote (4)J(F,H) coupling (F-C(alpha)-C(O)-N-H) of up to 4.2 Hz in alpha-fluoro amides with antiperiplanar arrangement of the C-F and the C O bonds (dihedral angle F-C-C=O ca. 180 degrees) confirms that previous NMR determinations, using the XPLOR-NIH procedure, of the secondary structures of beta-peptides containing beta(3)hAla(alpha F) and beta(3)hAla(alpha F-2) residues were correct. In contrast, molecular-dynamics (MD) simulations, using the GROMOS program with the 45A3 force field, led to an incorrect conclusion about the relative stability of secondary structures of these beta-peptides. The problems encountered in NMR analyses and computations of the structures of backbone-F-substituted peptides are briefly discussed.