Fluorine–hydrogen interactions observed in a helix structure having an orn-free gramicidin S sequence incorporating 4-<i>trans</i>-fluoroproline

The deca-peptide Boc-(d-Phe-tFPro-Val-Leu-Leu)₂-OMe (<b>1</b>) (Boc is <i>tert</i>-but-oxy-carbonyl, tFPro is 4-<i>trans</i>-fluoro-l-proline d-Phe is d-phenyl-alanine, Val is valine and Leu is leucine) crystallized in a methanol-solvated form (C₆₈H₁₀₄F₂N₁₀O₁₃·CH₄O). Peptide <b>1</b> has a sequence similar to gramicidin S (GS) incorporating tFPro. GS is a cyclic peptide, with the d-Phe-Pro unit known as a strong β-turn inducer in previous studies. Thus, it was initially assumed that <b>1</b> would bend at the d-Phe6-tFPro7 position, potentially forming a sheet-like structure. However, the structure of <b>1</b> was a helix, a surprising finding in GS-related structural studies. A factor enabling this helical formation could be the fluorine-H inter-actions between tFPro and the aromatic rings of d-Phe residues.