C₁₁/C₉ Helices in Crystals of αβ Hybrid Peptides and Switching Structures between Helix Types by Variation in the α‑Residue

Close-packed helices with mixed hydrogen bond directionality are unprecedented in the structural chemistry of α-polypeptides. While NMR studies in solution state provide strong evidence for the occurrence of mixed helices in (ββ)_<i>n</i> and (αβ)_<i>n</i> sequences, limited information is currently available in crystals. The peptide structures presented show the occurrence of C₁₁/C₉ helices in (αβ)_<i>n</i> peptides. Transitions between C₁₁ and C₁₁/C₉ helices are observed upon varying the α-amino acid residue

C₁₂ Helices in Long Hybrid (αγ)_<i>n</i> Peptides Composed Entirely of Unconstrained Residues with Proteinogenic Side Chains

Unconstrained γ⁴ amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (αγ)_<i>n</i> sequences. The C₁₂ helical conformation for the decapeptide, Boc-[Leu-γ⁴(<i>R</i>)­Val]₅-OMe, is established in crystals by X-ray diffraction. A regular C₁₂ helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu-γ⁴(<i>R</i>)­Val]₉-OMe, and a designed 16 residue (αγ)_<i>n</i> peptide, incorporating variable side chains. Unconstrained (αγ)_<i>n</i> peptides show an unexpectedly high propensity for helical folding in long polypeptide sequences

Unconstrained Homooligomeric γ‑Peptides Show High Propensity for C₁₄ Helix Formation

Monosubstituted γ⁴-residues (γ⁴Leu, γ⁴Ile, and γ⁴Val) form helices even in short homooligomeric sequences. C₁₄ helix formation is established by X-ray diffraction in homooligomeric (γ)_<i>n</i> tetra-, hexa- and decapeptide sequences demonstrating the high propensity of γ residues, with proteinogenic side chains, to adopt locally folded conformations