Conformation of the cyclic tetrapeptide dihydrochlamydocin. Iabu-L-Phe D-Pro-LX, and experimental values for 3 leads to 1 intramolecular hydrogen bonds by X-ray diffraction.

Chlamydocin, Iabu-L -Phe-D -Pro-L X, is a naturally occurring cyclic tetrapeptide that exhibits high cytostatic activity. The conformation of the peptide ring, as well as the stereo configuration in the vicinity of the epoxide ring, have been established by a single-crystal X-ray study of dihydrochlamydocin: C₂₈H₄₀N₄O₆·H₂O. It crystallizes in the monoclinic space group P2₁ with a = 12.616(6) Å, b = 12.355(6) Å, c = 9.442(5) Å, and β = 99.5(1)°. The structure was solved by the symbolic addition procedure for phase determination followed by the tangent formula method of phase refinement. This structure represents the first cyclic tetrapeptide in which all four peptide units have been found in the trans conformation; however, each peptide unit is significantly nonplanar with ω angles deviating by 14–24° from the ideal value of 180°. This molecule contains two intramolecular 3 → 1 hydrogen bonds and experimentally determined parameters for these seven-membered turns are presented.     

Observation of a sterically unfavorable side-chain conformation in a leucyl residue: Crystal and molecular structure of L-leucyl–L-leucine · DMSO solvate

The crystal structure of a dipeptide L -leucyl–L -leucine (C₁₂H₂₄N₂O₃) has been determined. The crystals are monoclinic, space group P2₁, with a = 5.434(4) Å, b = 15.712(7) Å, c = 11.275(2) Å, β = 100.41(1)°, and Z = 2. The crystals contain one molecule of dimethyl sulfoxide (DMSO) as solvent of crystallization for each dipeptide molecule. The structure has been solved by direct methods and refined to a final R index of 0.059 for 920 reflections (sinθ/λ ? 0.60 Å^?1) with I ? 2σ (I). The trans peptide unit shows substantial degree of non-planarity (Δω = 14°). The peptide backbone adopts an extended conformation with torsion angles of ψ₁ = 138(1)°, ω₁ = 166(1)°, ?₂ = ? 149.3(7)°, ψ₂₁ = 164.2(7)°, and ψ₂₂ = ? 15(1)°. For the first leucyl residue, the side-chain conformation is specified by the torsion angles ¹χ₁ = 176.7(7)°, ¹χ₂₁ = 62(1)°, ¹χ₂₂ = ? 177.4(8)°; the second leucyl residue adopts a Sterically unfavorable conformation with ²χ₁ = 61(1)°, ²χ₂₁ = 97(1)°, and ²χ₂₂ = ?151(1)°. The packing involves head-to-tail interaction of peptide molecules and segregation of polar and nonpolar regions. The DMSO molecule is strongly hydrogen bonded to the terminal NH group. © 1994 John Wiley & Sons, Inc.     

Design of Peptides Using α,β-Dehydro-residues: Synthesis,Crystal Structure and Molecular Conformation of N-Boc-L-Val-ΔPhe–ΔPhe-L-Ala-OCH3

To obtain general rules of peptide design using α,β-dehydro-residues, a sequence with two consecutive ΔPhe-residues, Boc-L -Val-ΔPhe–ΔPhe- L -Ala-OCH₃, was synthesized by azlactone method in solution phase. The peptide was crystallized from its solution in an acetone/water mixture (70:30) in space group P6₁ with a=b=14.912(3) Å, c= 25.548(5) Å, V=4912.0(6) ų. The structure was determined by direct methods and refined by a full matrix least-squares procedure to an R value of 0.079 for 2891 observed [I?3σ(I)] reflections. The backbone torsion angles ?₁=?54(1)°, ψ₁= 129(1)°, ω₁=?177(1)°, ?₂ =57(1)°, ψ₂=15(1)°, ω₂ =?170(1)°, ?₃=80(1)°, ψ₃ =7(2)°, ω₃=?177(1)°, ?₄ =?108(1)° and ψ^T₄=?34 (1)° suggest that the peptide adopts a folded conformation with two overlapping β-turns of types II and III′. These turns are stabilized by two intramolecular hydrogen bonds between the CO of the Boc group and the NH of ΔPhe³ and the CO of Val¹ and the NH of Ala⁴. The torsion angles of ΔPhe² and ΔPhe³ side chains are similar and indicate that the two ΔPhe residues are essentially planar. The folded molecules form head-to- tail intermolecular hydrogen bonds giving rise to continuous helical columns which run parallel to the c-axis. This structure established the formation of two β-turns of types II and III′ respectively for sequences containing two consecutive ΔPhe residues at (i+2) and (i+3) positions with a branched β-carbon residue at one end of the tetrapeptide.     

13C- and 1H-nmr evidence for all-cis peptide bonds in cyclic tetrapeptide cyclo(L-Pro-Sar)2

Conformations of the cyclic tetrapeptide cyclo(L -Pro-Sar)₂ in solution were studied by ¹H- and ¹³C-nmr spectrometry and model building. The nmr data provide definite evidence that this cyclic peptide exists chiefly in two conformations, namely, a C₂-symmetric conformation and an asymmetric structure. The former was demonstrated to be predominant in polar solvents (100% in Me₂SO-d₆). This structure contains all cis-peptide bond linkages and all trans′ Pro C^α?CO bonds. It represents the first cyclic tetrapeptide in which all four peptide bonds have been found in the cis-conformation. As the polarity of the solvent decreases, the population of C₂-symmetric conformers decreases (88% in CD₃CN and 65% in CDCl₃). At the same time, a minor asymmetric conformer, characterized by cis-cis-cis-trans peptide bond sequences (two cis Sar-Pro bonds, one cis Pro-Sar bond, and one trans Pro-Sar bond), is seen to increase (9% in CD₃CN and 30% in CDCl₃). A proposed predominant conformation in solution for cyclo(L -Pro-Sar)₂ was compared with a crystal structure, as reported in an accompanying paper. Both structures show striking overall similarities.     

Synthesis,and crystal and molecular structure of the 310-helical α,β-dehydro pentapeptide Boc-Leu-Phe-Ala-ΔPhe-Leu-Ome

α,β-Dehydro amino acid residues are known to constrain the peptide backbone to the β-bend conformation. A pentapeptide containing only one α,β dehydrophenylalanine (ΔPhe) residue has been synthesized and crystallized, and its solid state conformation has been determined. The pentapeptide Boc-Leu-Phe-Ala-ΔPhe-Leu-OMe (C₃₉H₅₅N₅O₈, M_w = 721.9) was crystallized from aqueous methanol. Monoclinic space group was P2₁, a = 10.290(2)°, b = 17.149(2)°, c = 12.179(2) Å, β = 96.64(1)° with two molecules in the unit cell. The x-ray (Mo K_α, λ = 0.7107A) intensity data were collected using a CAD4 diffractometer. The crystal structure was determined by direct methods and refined using least-squares technique. R = 4.4% and R_w = 5.4% for 4403 reflections having |F₀| ≥ 3σ(|F₀|). All the peptide links are trans and the pentapeptide molecule assumes 3₁₀-helical conformation. The mean ?,ψ values, averaged over the first four residues, are ?64.4°, ?22.4° respectively. There are three 4 → 1 intramolecular hydrogen bonds, characteristic of 3₁₀,-helix. In the crystal, the peptide helices interact through two head-to-tail. N? H? O intermolecular hydrogen bonds. The peptide molecules related by 2₁, screw symmetry form a skewed assembly of helices. © 1995 John Wiley & Sons, Inc.     

Design of peptides using α,β-dehydro-residues: Synthesis,crystal structure and molecular conformation of Boc-L-Val- ΔPhe-ΔPhe-L-Val-OCH3

The peptide Boc-L-Val-ΔPhe-ΔPhe-L-Val-OCH₃ was synthesized by the azlactone method in solution phase, and its crystal and molecular structures were determined by x-ray diffraction method. Single crystals were grown by slow evaporation from a methanol/water solution at 6°C. The crystals belong to an orthorhombic space group P2₁2₁2₁ with a = 10.478 (6) Å, b = 13.953 (1), c = 24.347 (2) and Z = 4. The structure was determined by direct methods and refined by least squares procedure to an R value of 0.052. The structure consists of a peptide and a water molecule. The peptide adopts two overlapping β-turn conformations of Types II and I′ with torsion angles: ϕ₁ = -54.8 (6), ψ₁ = 130.5 (4), ϕ₂ = 65.8 (5), ψ₂ = 12.8 (6), ϕ₃ = 79.4 (5), ψ₃ = 3.9 (7)°. The conformation is stabilized by intramolecular hydrogen bonds involving Boc CO and NH of ΔPhe³ and CO of Val¹ and NH of Val⁴. The molecules are tightly packed in the unit cell. The crystal structure is stabilized by hydrogen bonds involving NH of ΔPhe² and CO of a symmetry related (x-½, ½ -y, -z) ΔPhe². The solvent-water molecule forms two hydrogen bonds with peptide molecule involving NH of Val¹ as an acceptor and another with CO of a symmetry related (1 -x, y-½, ½ -z) ΔPhe³ as a donor. These studies indicate that a tetrapeptide with two consecutive ΔPhe residues sequenced with valines on both ends adopts two overlapping β-turns of Types II and I′. © 1996 John Wiley & Sons, Inc.     

The crystal structure of d-glucose 6-(sodium hydrogen-phosphate)

The title compound, when recrystallised from water, is monoclinic, space group P2₁, with a = 5.774(4), b = 7.189(5), c = 12.69(1) Å, β = 106.66(5)°, and Z = 2. The crystal structure was determined from three-dimensional X-ray diffraction data taken on an automatic diffractometer with CuKα, and refined by least-squares techniques to R = 0.034 for 977 reflexions. The pyranose ring adopts the ⁴C₁ conformation. The conformation about the exocyclic C-5-C-6 bond is gauche-trans [the torsion angles O-6-C-6-C-5-O-5 and O-6-C-6-C-5-C-4 are 64.2(8) and ?175.6(7)°, respectively], which is significantly different from the gauche-gauche geometry in d-glucose 6-(barium phosphate). The phosphate ester bond, P-O-6, is 1.584(3) Å. All of the oxygen-bonded hydrogen atoms are involved in intermolecular hydrogen-bonds.     

Crystallographic characterization of the α,γ C12 helix in hybrid peptide sequences

The solid‐state conformations of two αγ hybrid peptides Boc‐[Aib‐γ⁴(R)Ile]₄‐OMe 1 and Boc‐[Aib‐γ⁴(R)Ile]₅‐OMe 2 are described. Peptides 1 and 2 adopt C₁₂‐helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C₁₂ motifs. The structure of peptide 2 reveals the formation of eight successive C₁₂ hydrogen‐bonded turns. Average backbone dihedral angles for αγ C₁₂ helices are peptide 1 , Aib; φ (°) = ?57.2 ± 0.8, ψ (°) = ?44.5 ± 4.7; γ⁴(R)Ile; φ (°) = ?127.3 ± 7.3, θ₁ (°) = 58.5 ± 12.1, θ₂ (°) = 67.6 ± 10.1, ψ (°) = ?126.2 ± 16.1; peptide 2 , Aib; φ (°) = ?58.8 ± 5.1, ψ (°) = ?40.3 ± 5.5; ψ⁴(R)Ile; φ (°) = ?123.9 ± 2.7, θ₁ (°) = 53.3 θ 4.9, θ ₂ (°) = 61.2 ± 1.6, ψ (°) = ?121.8 ± 5.1. The tendency of γ⁴‐substituted residues to adopt gauche–gauche conformations about the C^α–C^β and C^β–C^γ bonds facilitates helical folding. The αγ C₁₂ helix is a backbone expanded analog of α peptide 3₁₀ helix. The hydrogen bond parameters for α peptide 3₁₀ and α‐helices are compared with those for αγ hybrid C₁₂ helix. Copyright © 2016 European Peptide Society and John Wiley & Sons.     

X-Pro peptides: Solution and solid-state conformation of benzyloxycarbonyl-(Aib-Pro)2methyl ester,a type I β-turn

The synthesis of the tetrapeptide benzyloxycarbonyl(α-aminoisobutyryl-L -prolyl)₂-methyl ester (Z-(Aib-Pro)₂-OMe) and an analysis of its conformation in solution and the solid state are reported. Stepwise synthesis using dicyclohexylcarbodiimide leads to racemization at Pro(2). Evidence for the presence of diastereomeric tetrapeptides is obtained from 270-MHz¹H-nmr and 67.89-MHz ¹³C-nmr. The all-L tetrapeptide is obtained by fractional crystallization from ethyl acetate. The NH of Aib(3) is shown to be involved in an intramo-lecular hydrogen bond by variable-temperature ¹H-nmr and the solvent dependence of NH chemical shifts. The results are consistent with a β-turn conformation with Aib(1) and Pro(2) at the corners stabilized by a 4 → 1 hydrogen bond. The molecule crystallizes in the space group P2₁2₁2₁, with a = 8.839, b = 14.938, and c = 22.015 Å. The structure has been refined to an R value of 0.051. The peptide backbone is all-trans, and a 4 → 1 hydrogen bond, between the CO group of the urethane moiety and Aib(3) NH, is observed. Aib(1) and Pro(2) occupy the corner positions of a type I β-turn with ? = ?55.4°, Ψ = ?31.3° for Aib(1) and ? = ?71.6°, Ψ = ?38° for Pro(2). The tertiary amide unit linking Pro(2) and Aib(3) is significantly distorted from planarity (Δω = 14.3°).     

Crystal and molecular structure of benzyloxycarbonyl-α-aminoisobutyryl-L-prolyl methylamide: The observation of an X2-Pro3 Type III β-Turn

The crystal and molecular structure of N-benzyloxycarbonyl-α-aminoisobutyryl-L -prolyl methylamide, the amino terminal dipeptide fragment of alamethicin, has been determined using direct methods. The compound crystallizes in the orthorhombic system with the space group P2₁2₁2₁. Cell dimensions are a = 7.705 Å, b = 11.365 Å, and c = 21.904 Å. The structure has been refined using conventional procedures to a final R factor of 0.054. The molecular structure possesses a 4 → 1 intramolecular N-H—O hydrogen bond formed between the CO group of the urethane moiety and the NH group of the methylamide function. The peptide backbone adopts the type III β-turn conformation, with ?₂ = ?51.0°, ψ₂ = ?39.7°, ?₃ = ?65.0°, ψ₃ = ?25.4°. An unusual feature is the occurrence of the proline residue at position 3 of the β-turn. The observed structure supports the view that Aib residues initiate the formation of type III β-turn conformations. The pyrrolidine ring is puckered in C^γ-exo fashion.     

The Structure of Neplanocin C

Abstract

The molecular and crystal structure of neplanocin C(3), C₁₁H₁₃N₅O₄ M.W. = 279.26, has been determined by X-ray anlys?s. The space group is P2₁ with a=16.381(2), b=8.210(1), c=9.127(1) Å, β=105.31(1)° and z=4. The structure was solved by direct method, and least-squares refinement using 2093 reflections with |Fo|>3σ(F) led to the final R value of 0.0772. The sugar puckering of the two crystal-lographically independent molecules is C(2′)-exo-C(3′)-endo, and the torsion angles about the N(9)-C(1′) bond are 22.8(6) and 28.7(6)°, respectively (anti conformation).     

Chain length dependent transition of 310- to α-helix of Boc-(Ala-Aib)n-OMe

An apolar synthetic octapeptide, Boc-(Ala-Aib)₄-OMe, was crystallized in the triclinic space group P1 with cell dimensions a = 11.558 Å, b = 11.643 Å, c = 9.650 Å, α = 120.220°, β = 107.000°, γ = 90.430°, V = 1055.889 ų, Z = 1, C₃₄H₆₀O₁₁N₈·H₂O. The calculated crystal density was 1.217 g/cm³ and the absorption coefficient ? was 6.1. All the intrahelical hydrogen bonds are of the 3₁₀ type, but the torsion angles, ? and ψ, of Ala(5) and Ala(7) deviate from the standard values. The distortion of the 3₁₀-helix at the C-terminal half is due to accommodation of the bulky Boc group of an adjacent peptide in the nacking. A water molecule is held between the N-terminal of one peptide and the C-terminal of the other. The oxygen atom of water forms hydrogen bonds with N (1) -H and N (2) -H, which are not involved in the intrahelical hydrogen bonds. The hydrogen atoms of water also formed hydrogen bonds with carbonyl oxygens of the adjacent peptide molecule. On the other hand, ¹H-nmr analysis revealed that the octapeptide took an α-helical structure in a CD₃CN solution. The longer peptides, Boc-(Ala-Aib)₆-OMe and Boc-(Ala-Aib)₈-OMe, were also shown to take an α-helical structure in a CD₃CN solution. An α-helical conformation of the hexadecapeptide in the solid state was suggested by x-ray analysis of the crystalline structure. Thus, the critical length for transition from the 3₁₀- to α-helix of Boc-(Ala-Aib)_n-OMe is 8. © 1993 John Wiley & Sons, Inc.     

Type II β-turn conformation of pivaloyl-L-prolyl-α-aminoisobutyryl-N-methylamide: Theoretical,spectroscopic, and X-ray studies

Pivaloyl-L -Pro-Aib-N-methylamide has been shown to possess one intramolecular hydrogen bond in (CD₃)₂SO solution, by ¹H-nmr methods, suggesting the existence of β-turns, with Pro-Aib as the corner residues. Theoretical conformational analysis suggests that Type II β-turn conformations are about 2 kcal mol^?1 more stable than Type III structures. A crystallographic study has established the Type II β-turn in the solid state. The molecule crystallizes in the space group P2₁ with a = 5.865 Å, b = 11.421 Å, c = 12.966 Å, β = 97.55°, and Z = 2. The structure has been refined to a final R value of 0.061. The Type II β-turn conformation is stabilized by an intramolecular 4 → 1 hydrogen bond between the methylamide NH and the pivaloyl CO group. The conformational angles are ?_Pro = ?57.8°, ψ_Pro = 139.3°, ?_Aib = 61.4°, and ψ_Aib = 25.1°. The Type II β-turn conformation for Pro-Aib in this peptide is compared with the Type III structures observed for the same segment in larger peptides.     

Experimental conformational study of two peptides containing α-aminoisobutyric acid. Crystal structure of N-acetyl-α-aminoisobutyric acid methylamide

Some theoretical studies have predicted that the conformational freedom of the α-aminoisobutyric acid (H-Aib-OH) residue is restricted to the α-helical region of the Ramachandran map. In order to obtain conformational experimental data, two model peptide derivatives, MeCO-Aib-NHMe 1 and Bu^tCO-LPro-Aib-NHMe 2 , have been investigated. The Aib dipeptide 1 crystallizes in the monoclinic system (a = 12.71 Å, b = 10.19 Å, c = 7.29 Å, β = 110.02°, Cc space group) and its crystal structure was elucidated by x-ray diffraction analysis. The azimuthal angles depicting the molecular conformation (? = ?55.5°, ψ = ?39.3°) fall in the α-helical region of the Ramachandran map and molecules are hydrogen-bonded in a three-dimensional network. In CCl₄ solution, ir spectroscopy provides evidence for the occurrence of the so-called ₅ and C₇ conformers stabilized by the intramolecular i → i and i + 2 → i hydrogen bonds, respectively. The tripeptide 2 was studied in various solvents [CCl₄, CD₂Cl₂, CDCl₃, (CD₃)₂SO, and D₂O] by ir and pmr spectroscopies. It was shown to accommodate predominantly the βII folded state stabilized by the i + 3 → i hydrogen bond. All these experimental findings indicate that the Aib residue displays the same conformational behavior as the other natural chiral amino acid residues.     

Helix-Forming tendencies of amino acids depend on their sequence contexts: Tripeptides AFG and FAG show incipient β-bulge formation in their crystal structures

Many of the theoretical methods used for predicting the occurrence of α-helices in peptides are based on the helical preferences of amino acid monomer residues. In order to check whether the helix-forming tendencies are based on helical preferences of monomers only or also on their sequence contexts, we synthesized permuted sequences of the tripeptides GAP, GAV, and GAL that formed crystalline helices with near α-helical conformation. The tripeptides AFG and FAG formed good crystals. The x-ray crystallographic studies of AFG and FAG showed that though they contain the same amino acids as GAF but in different sequences, they do not assume a helical conformation in the solid state. On the other hand, AFG and FAG, which contain the same amino acids but in a different sequence, exhibit nearly the same backbone torsion angles corresponding to an incipient formation of a β-bulge, and exhibit nearly identical unit cells and crystal structures. Based on these results, it appears that the helix-forming tendencies of amino acids depend on the sequence context in which it occurs in a polypeptide. The synthetic peptides AFG (L -Ala-L -Phe-Gly) and FAG (L -Phe-L -Ala-Gly), C₁₄H₁₉N₃O₄, crystallize in the orthorhombic space group P2₁2₁2₁, with a = 5. 232(1), b = 14. 622(2), c = 19. 157(3) Å, D_x = 1.329 g cm^?3, Z = 4, R = 0.041 for 549 reflections for AFG, and with a = 5. 488(2), b = 14.189 (1), c = 18.562(1) Å, D_x = 1.348 g cm^?3, Z = 4, R = 0.038 for 919 reflections for FAG. Unlike the other tripeptides GAF, GGV, GAL, and GAI, the crystals of AFG and FAG do not contain water molecule, and the molecules of AFG or FAG do not show the helical conformation. The torsion angles at the backbone of the peptide are ψ₁ = 144. 5(5)°; ?₂, ψ₂ = ?98.1(6)°, ?65.2(6)° ?₃, ψ₁₃, ψ₃₁ = 154.1(6)°, ?173.6(6)°, 6.9(8)° for AFG; and ψ₁ = 162.6(3)°; ?₂, ψ₂ = ?96.7(4)°, ?46.3(4)°; ?₃, ψ₁₃, ψ₃₁ = 150.1(3)°, ?168.7(3)°, 12.2(5)° for FAG. The conformation angles (? ψ) for residues 2 and 3 for both AFG and FAG show incipient formation of an β-bulge. © 1993 John Wiley & Sons, Inc.     

A conformational study of the tetrapeptide CH3CO-Ala-Asp-Gly-Lys-NHCH3 corresponding to a β-bend in staphylococcal nuclease

The tetrapeptide sequence Ala-Asp-Gly-Lys occurs as a type I′ β-bend at residues 94–97 in staphylococcal nuclease. We have synthesized theN-acetyl,N′-methylamide derivative of this tetrapeptide and studied its conformation in solution, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. In the synthesis, special attention was paid to the possibility of cyclic aspartimide formation giving rise to mixtures of α- and β-Asp-Gly products. The presence of such a mixture was excluded by infrared, NMR, and other analytical procedures applied to the products and to models for α- and β-linked aspartyl residues. The CD spectra of the protected tetrapeptide in water, methanol, and trifluoroethanol show no evidence of preferred chain conformations. In dimethylsulfoxide-d ₆ , however, the NMR spectra are consistent with the presence of a population of conformers in which the Lys and C-terminal NHCH₃ amide protons are shielded from solvent. Taken together with the observed³J_NH-C ^α _H coupling constants for all residues, this permitted the construction and energetic evaluation of possible conformations in solution. Only one such conformation was fully compatible with the NMR data; this is a type II β-bend in which the Lys and C-terminal NHCH₃ amide protons are close to the Ala C=O group and may form bifurcated hydrogen bonds with it. This conformation can be converted into the conformation existing in staphylococcal nuclease by rotating the plane of the Ala-Asp peptide group by about 120° around a line connecting the Ala and Asp C_α atoms and by making small shifts in dihedral angles elsewhere in the peptide.     

Conformation of cyclic dipeptides from empirical energy calculations

Empirical energy calculations on cyclo-Gly-X with X- Phe, Tyr, Val, and Leu as a function of the side-chain torsion angles χ indicate that the conformation of minimum energy are characterized by χ₁ = 60°, χ² = 90° for Phe and Try, χ¹ = ?60° for Val and χ¹ = ?60°, χ² = 180° and χ¹ = 60° and χ² = 150° for Leu. The minimum energy conformation of cyclo-Gly-Phe and cyclo-Gly-Val have the side chains of Phe and Val stacked over the poperazinedione ring as suggested by NMR and found for cyclo-Gly-Tyr crystal structure. In contrast, the Leu side chain is expected to exist in an extended or a quasi-folded form.     

Solid-state conformations of α-Aminoisobutyryl-L-prolyl sequences: Crystal structure of Boc-Aib-L-Pro-OBzl

The protected dipeptide Boc-Aib-Pro-OBzl, C₂₁H₃₀N₂O₅, crystallizes in the orthorhombic space group P2₁2₁2₁, with a = 12.820, b = 10.529, c = 16.548Å, and Z = 4. The crystal structure has been solved by direct methods and refined to an R value of 0.074 for 1352 reflections. The Boc-Aib-Pro-OBzl molecule has been shown to adopt an unfolded conformation in the solid state with ?_Aib = 50.5°, Ψ_Aib = 45.3°, ?_Pro = ?64.6°, and Ψ_Pro = 148.1°. The result is in marked contrast with the reported crystal structure of Cbz-Aib-Pro-NHMe, which adopts an intramolecularly hydrogen-bonded β-turn conformation. Comparison with 13 reported conformations of Aib-Pro sequences in the crystalline state revealed that the Aib-Pro sequence adopts an unfolded conformation if the residue that immediately follows the dipeptide sequence possesses no hydrogen available for hydrogen bonding, while a β-turn conformation is preferred if the Pro residue is followed by an NH group. Correlation between pyrrolidine ring puckering of the Pro residue and main-chain conformation in Aib-Pro sequences is discussed.     

Interaction of a phosphorylated site of muscle phosphofructokinase with the activation of the enzyme by NH4+ and K+.1

The crystal structure of the cyclic peptide disulfide

has been determined by X-ray diffraction. The peptide crystallizes in the space group P2₁2₁2₁, with a = 8.646(1), b = 18.462(2), c = 19.678(3)Å and Z = 4. The molecules adopt a highly folded compact conformation, stabilized by two intramolecular 4→ 1 hydrogen bonds between the Cys (1) and Pro (2) CO groups and the Cys (4) and methylamide NH groups, respectively. The backbone conformational angles for the peptide lie very close to those expected for a 3₁₀ helix. The S-S bridge adopts a right handed twist with a dihedral angle of 82°. The structure illustrates the role of stereochemically constrained residues, in generating novel peptide conformations.     

Peptide design 310-helical conformation of a linear pentapeptide containing two dehydrophenylalanines,Boc-Gly-ΔZPhe-Leu-ΔZPhe-Ala-NHCH3

α, β-Dehydroamino acids are expected to provide conformational constraint to the peptide backbone. A pentapeptide containing two dehydrophenylalanines (Δ^ZPhe) separated by one L -amino acid has been synthesized and its solid state conformation determined. The pentapeptide, Boc-Gly-Δ^ZPhe-Leu-Δ^ZPhe-Ala-NHCH₃, crystallizes from aqueous methanol in the orthorhombic space group P2₁2₁2₁. There are four formula units, C₃₅H₄₆N₆O₇, in a unit cell of dimensions a = 10.155(3), b = 15.175(1), and c = 23.447(2) Å, at room temperature. The structure was solved by direct methods program, SIR88, and refined to a final R = 0.038 based on 3049 reflections with I > 2σ(I). All the peptide links are trans and the backbone conformation of the pentapeptide can be described as a 3₁₀-helix, with mean ?, ψ values of ?65.1° and ?22.8° (the value is averaged over the first four residues). There are four intramolecular 4 → 1 type hydrogen bonds characteristic of 3₁₀-type helices. In the crystal, the helices are held together by intermolecular N? H…?O?C head-to-tail and lateral hydrogen bonding between symmetry related molecules. This mode of packing is similar to the packing motifs observed so often in other oligopeptides that adopt a 3₁₀-helical structure. © 1993 John Wiley & Sons, Inc.