The Effect of Backbone‐Heteroatom Substitution on the Folding of Peptides – A Single Fluorine Substituent Prevents a β‐Heptapeptide from Folding into a 314‐Helix (NMR Analysis)

摘要: The β-heptapeptides H-βhVal-βhAla-βhLeu-βhAla(Xn)-βhVal-βhAla-βhLeu-OH 3–7 with central 3-amino-2-fluoro-, 3-amino-2,2-difluoro-, or 3-amino-2-hydroxybutanoic acid residues (βhAla(Xn)) of like and unlike configuration were subjected to a detailed NMR analysis in MeOH solution. For the geminal difluoro for F- OH-substituted derivatives u-configuration (see 5, 4, 7, resp.), 14-helices found, i.e., axial disposition hetero atoms on helix. two compounds containing l-configured β-amino moieties 3 6) are not helical over full lengths chains; they have ‘quasi-helical’ termini turn consisting ten-membered H-bonded ring (Fig. 2, d e). Quantum-mechanical calculations l- u-AcNH-CHMe-CHF-CONH2 confirm observed preference conformation antiperiplanar arrangement FC CO bond. calculated energy difference between ‘non-helical’ geometry this moiety hypothetical one is 6.4 kcal/mol (Fig. 3).