Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I' beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide.

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I'beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 --> 1 hydrogen bonds. In addition, a single 4 --> 1 hydrogen bond is also observed at the N-terminus. All five Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C(alpha)-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean tau values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively.

Peptide helices with pendant cycloalkane rings. Characterization of conformations of 1-aminocyclooctane-1-carboxylic acid (Ac8c) residues in peptides.

A pentapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-OMe 1, an octapeptide, Boc-Leu-Ac8c-Ala-Leu-Ac8c-Ala-Leu-Ac8c-OMe 2 and a tripeptide, Boc-Aib-Ac8c-Aib-OMe 3 containing the 1-aminocyclooctane-1-carboxylic acid residue (Ac8c) were synthesized and conformationally characterized by x-ray diffraction studies in the crystal state. Peptides 1 and 2 were also studied by NMR in CDC13 solution. Peptide 1 adopts a purely 3(10)-helical conformation in crystals, stabilized by three intramolecular 1 <-- 4 hydrogen bonds. Peptide 2 in crystals is largely 3(10)-helical with distortion in the backbone at the N-terminus by the insertion of a water molecule between Ac8c (2) CO and Ala (6) NH groups. Peptide 3 forms a C10-ring structure, i.e. a type III (III') beta- turn conformation stabilized by an intramolecular 1 <-- 4 hydrogen bond. Five cyclooctane rings assume boat-chair conformations, whereas the sixth [Ac8c(8) in 2] is appreciably distorted, resembling a chiral intermediate in the pseudorotational pathway from the boat-chair to the twisted boat-chair conformation. Internal bond angles of the cyclooctane rings are appreciably distorted from the tetrahedral value, a characteristic feature of the cyclooctane ring. Peptide 1 crystallized in the space group P212121 with a = 11.900(4) A, b = 18.728(6) A, c = 20.471(3) A and Z = 4. The final R1 and wR2 values are 0.0753 and 0.2107, respectively, for 3901 observed reflections [Fo > or = 3 sigma (Fo)]. Peptide 2 crystallized in space group P21 with a = 12.961(5) A, b = 17.710(10) A, c = 15.101(7) A, beta = 108.45(4) degrees and Z = 2. The final R1 and wR2 values are 0.0906 and 0.1832, respectively, for 2743 observed reflections [Fo > or = 3sigma (Fo)]. 1H-NMR studies on both the peptides strongly suggest the persistence of 3(10)-helical conformations in solution. Peptide 3 crystallized in the space group P21/n, with a = 10.018(1) A, b = 20.725(1) A, c = 12.915(1) A and Z = 4. The final R1 and wR2 values are 0.0411 and 0.1105, respectively, for 3634 observed reflections [Fo > or = 4sigma (Fo)].