Insertion of achiral ω-amino acids into peptide sequences results in replacement of scissile peptide bonds by proteolytically stable C−C bonds. This provides a convenient means of creating peptidomimetics. The present study establishes the preservation of helical structures in octa- and undecapeptides with centrally located β- and γ-amino acids in the sequence. X-ray diffraction analyses of single crystals and NMR studies have been used to investigate the extent of perturbations of a regular 310- or α-helix by the introduction of (−CH2−) n groups into the backbone by the use of the β-Ala-γ-Abu segment (β-Ala = β-alanine, γ-Abu = γ-aminobutyric acid), which is formally homomorphous with a (Gly)3 segment. In crystals, the octapeptide Boc-Leu-Aib-Val-β-Ala-γ-Abu-Leu-Aib-Val-OMe (1) and the undecapeptide Boc-Leu-Aib-Val-β-Ala-γ-Abu-Leu-Aib-Val-Ala-Leu-Aib-OMe (2) retain their helical motifs with minor bulges. Five new types of 4 → 1, 5 → 1, and 6 → 1 hydrogen bond rings are formed with up to three extra CH2 moieties. Cell parameters for peptide 1 are space group P212121 with a = 11.506 (1) Å, b = 16.600 (1) Å, c = 27.362(1) Å, and R = 6.1% for 2696 data measured >4σ(F); for the undecapeptide 2, the space group is P21 with a = 8.605 (3) Å, b = 22.806 (4) Å, c = 19.014 (3) Å, β = 101.47(2)°, and R = 7.5% for 3797 data measured >4σ(F). Helical conformations in solution are also maintained for peptide 2 as is evident from NMR studies in CDCl3, which suggest that the centrally positioned, flexible β-Ala-γ-Abu segment can be comfortably accommodated into helical structures adopting gauche conformations about specific C−C bonds of the poly(methylene) units. Twenty structures for backbone conformations generated from MD simulations using NMR-derived contraints, superpose with a low RMSD value (0.78 ± 0.05 Å), further indicating that in these peptides the conformational flexibility of the β-Ala-γ-Abu segment is limited and confined to largely helical conformations.

Batrachotoxinin A, a venom from the Colombian poison arrow frog, Phyllobates aurotaenia, has been established by means of an X-ray analysis of the O-p-bromobenzoate derivative, to be 3e,9~-epoxy-14fl, 18/?-[epoxyethano-N-methylimino]-5/~-pregna-7,16-diene-3/?, 11~, 20~-triol. The material crystallizes in space group P21212a with a= 15.42, b = 7"05 and c= 26.50/~. The specialized position of the Br atom (at x, 0, 0) and the severely restricted amount of data limited the information which was available from use of the heavy atom phases. The structure was deduced by use of the tangent formula in a recycling procedure applied to partial structural information.