Crystal structure and conformation of a highly constrained linear tetrapeptide Boc-Leu-dehydro Phe-Ala-Leu-OCH3

The conformation of a tetrapeptide containing a dehydro amino acid, Δ^zPhe, in its sequence has been determined in the crystalline state using X-ray crystallographic techniques. The tetrapeptide, Boc-Leu-Δ^zPhe-Ala-Leu-OCH₃, crystallizes in the orthorhombic space group P2₁2₁2₁ with four molecules in a unit cell of dimensions a = 11.655(1) Å, b = 15.698(6) Å and c = 18.651(3) Å V = 3414.9 Å and Dcalc =1.12 g/cm ^?3. The asymmetric unit contains one tetrapeptide molecule, C₃₀H₄₆N₄O₇, a total of 41 nonhydrogen atoms. The structure was determined using the direct methods program SHELXS86 and refined to an R-factor of 0.049 for 3347 reflections (13.0(I). The linear tetrapeptide in the crystal exhibits a double bend of the Type III-I, with Leu¹ (<φ=?54.1°, Ψ=?34.5°) and Δ^zPhe² (φ=?59.9°, Ψ=?17.1°) as the corner residues of Type III turn and Δ^zPhe² (φ=?59.9°, Ψ=?17.1°) and Ala³ (φ=?80.4°, Ψ= 0.5°) residues occupying the corners of Type I turn, with Δ^zPhe as the common residue in the double bend. The turn structures are further stabilized by two intramolecular 4→1 type hydrogen bonds.     

Synthesis and properties of chemotactic peptide analogs I. Crystal structure and molecular conformation of HCO-Met-Leu-Ain-OMe

HCO-Met-Leu-Ain-OMe (2), an analog of the chemotactic peptide HCO-Met-Leu-Phe-OH, containing the conformationally blocked residue of the 2-aminoindane-2-carboxylic acid (Ain) has been synthesized and its crystal and molecular conformation has been determined. Crystals of 2 are monoclinic, space group P2₁, with a = 15.059(7), b = 18.548(7), c = 9.600(4)Å;β= 85.04(3). The structure has been solved by direct methods and refined to R = 0.069 for 2813 independent reflections with I > 2.5σ(I). Two independent molecules A and B have been found in the asymmetric unit of the crystal of 2. Their conformation can be described as extended at the Met and Leu residues, but folded at the C-terminal Ain residue. The helical folding is left- and right-handed in the A and B molecule, respectively. The crystal packing is characterized by ribbons of intermolecular hydrogen bonded molecules extended along the c direction. The constrained analog 2 is highly active in the superoxide production, thus indicating that a stabilization of a helical folding at the C-terminal region of chemotactic tripeptides maintains the activity. The orientation of the aromatic ring, with respect to its adjacent backbone atoms, does not seem critical for the activity.     

Crystal structure analysis of a β-turn mimic in hydrazino peptides

The crystal structures of four hydrazino peptides (Piv-Pro-h(N^α-Bzl)Gly-NHiPr 1 , Piv-Pro-hAla-NHiPr 2 , Moc-hPro-NHiPr 3 , and Boc-hPro-Gly-N(OH)Me 4 ) deriving from the hydrazino analogues of glycine (hGly), l -alanine (hAla) or l -proline (hPro) have been solved. They reveal a common folded structure of the α-hydrazino acid residue characterized by a bifurcated hydrogen bond closing an eight-membered cycle. This folded structure is topologically similar to the βII′-turn in peptides, and the CO-NH-N hydrazide link can be considered as a good turn-inducer in peptide analogues.     

Crystal and molecular structure of the dehydropeptide Ac-ΔPhe-Val-ΔPhe-NH-Me

The dehydropeptide Ac-ΔPhe-l -Val-ΔPhe-NH-Me, containing two dehydrophenylalanine (ΔPhe) residues, crystallizes from methanol/water in space group P2₁2₁2₁ with a= 12.622 (1), b= 12.979 (1), and c= 15.733 (1) Å. In the solid state, the molecular structure is characterized by the presence of two intramolecular hydrogen bonds which form two consecutive β-bends. The (φ,Ψ) torsion angles of the three residues are very similar and close to the standard values of type III β-bends, so the molecular conformation corresponds to an incipient right-handed 3₁₀ -helix, only slightly distorted. In the crystal, the molecules are linked by head-to-tail hydrogen bonds, thus forming continuous helical columns packed in antiparallel mode. There are no lateral hydrogen bonds; the only interactions are hydrophobic contacts between the apolar side chains of neighboring helical columns.     

Crystal and molecular structure of L-lysyl-L-valine hydrochloride – a new lysine conformation

Thin plates of L-lysyl-L-valine hydrochloride (C₁₁H₂₄N₃O₃Cl) were obtained using the vapour diffusion technique and analysed by X-ray diffraction. The unit cell is orthorhombic, space group P2₁2₁2₁, a = 5.465(6)Å, b = 19.657(4) Å, c = 13.522(2) Å, V = 1452.6(2.1) ų and Z = 4. The structure was solved by direct methods and refined to an agreement factor of 6.7% for 939 reflections with I > 3 σ(I). The lysine side chain conformation (g^- g^- tt) has never been found in peptide crystal structures, although it has been reported to occur in proteins. A network of hydrogen bonds between peptide molecules spreads along the a and c directions while no direct bonds are observed to occur between peptides along the b axis direction. This asymmetric pattern of interactions correlates with the crystal morphology.     

Crystal and molecular structure of N-α-acetyl-L-arginine-methyl ester hydrochloride

The crystal structure of N-α-acetyl-L-arginine-methyl ester hydrochloride has been determined from X-ray diffraction data. The crystals are orthorhombic, space group P2₁2₁2₁, a = 15.746 (4), b = 11.569 (4), c = 7.158 (3) Å, Z = 4. The structure was solved by direct methods (MULTAN) and refined by fullmatrix least-squares to an R = 0.070 for all observed reflections. The molecule shows a planar peptidic unit, with a distortion of H(N1) due to hydrogen bond interaction. The side chain is in the low energy all-trans conformation. The guanidinium group forms three hydrogen bonds with the carbonyl oxygens of two neighbouring molecules. A direct interaction of the peptidic NH with the chloride ions is observed. The latter ions also interact with the guanidinium groups, neutralizing their charges.     

Crystal structure and conformation of l-pyroglutamyl-l-alanine

Crystals of the dipeptide, pyroglutamyl-alanine (C₈H₁₂N₂O₄) grown from aqueous methanol are monoclin-ic, space group P2₁ with the following cell parameters: a = 4.863(2), b = 16.069(1), c = 6.534(2)Å and β= 109.9(2)°, V = 480.0ų, M_r= 200.2, D_c= 1.385 g cm^?3, and Z = 2. The crystal structure was solved by the application of direct methods and refined to an R value of 0.044 for 699 reflections with I > 2σ. The amide of the pyroglutamyl side chain is cis, ω₁= 2.6(7)°; the peptide unit is trans and appreciably non-planar (ω₂= 167.4(5)°). The backbone torsional angles are: Ψ₁= 166.1(5), φ₂=?90.3(6), and Ψ₂=?22.4(6)°. This structure contains a short (2.551(5)Å) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most acyl amino acids and acyl peptides.     

A β-turn-like conformation in “reduced” peptides Crystal structures of two dipeptide analogs with Pro-GlyΨ[CH2-NH] sequence

The conformational properties of the “reduced” dipeptides tBuCO-Pro-GlyΨ[CH₂-NH]NRR′(R = H, R = Et; R = R′= Me) greatly depend upon the neutral or protonated state of the “reduced” amide bond. Due to protonation, the quite flexible neutral molecule turns into a very stable conformation resembling a β-turn in both the solid and solute states. The existence of a strong N ⁺—H…O=C interaction closing a 10-membered cycle illustrates the possible specific properties induced by a chemical modification in pseudopeptide analogs.     

Crystal molecular structures of two tripeptides related to the sequence coding for N-glycosylation

The crystal structures of two tripeptides related to the sequence coding for N-glycosylation of peptides have been solved: Boc-Asn(Me)-Ala-Ser-OMe, 1, and Boc-Asn(Me)-Pro-Ser-NHMe, 2. Both molecules contain an “Asx-turn” characterized by a hydrogen bond between the Ser-NH and Asn-CγOγ sites. Moreover, the Pro-Ser sequence is βI-folded in 2. The Ser hydroxyl group is also intramolecularly hydrogen-bonded in both molecules, but two different hydrogen bondings are observed. In 1, the Ser-Oγ H bond interacts with the Asn-CγOγ carbonyl, in good agreement with one of the mechanisms which have been proposed for the N-glycosylation of peptides. In 2, the Ser-OγH bond turns out to be involved in an intra-residue interaction with Ser-C'O, and this conformational change is essentially the consequence of chemically different C-terminus functions.     

Crystal structure of deltakephalin: a γ-selective opioid peptide with a novel β-bend-like conformation

The solid-state structure of deltakephalin (Tyr-D Thr-Gly-Phc-Leu-Thr) has been determined by single-crystal X-ray diffraction. Deltakephalin (DTLET) is a synthetic opioid peptide which differs from enkephalin in that a d -Thr has been substituted for Gly² and a sixth residue, l -Thr, has been added. Clear colorless plates obtained using vapor diffusion and macro-seeding crystallization techniques were monoclinic; space group C2 with u = 27.389(5), b = 9.205(2), c = 16.788(2) Å, β= 98.87(2) ˚ and V= 4181.4(14) ų. The asymmetric unit contained one molecule of DTLET and six molecules of water, giving a calculated density of 1.28 g cm⁻³. The crystal structure revealed that DTLET has a pseudo type I'β-bend which is stabilized by an intramolecular side-chain to backbone hydrogen bond. This is the first reported observation of a pseudo β-bend conformation in a solid-sate structure of an enkephalin analog.     

Crystal structure,conformation, and potential energy calculations the chemotactic peptide N- formyl-l-Met-l-Leu-l-Phe-OMe

The tripeptide N-formyl-L-Met-l -Leu-l -Phe-OMe (FMLP-OMe) crystallizes in the orthorhombic system, space group P 2₁2_l2₁, with the following unit-cell parameters: a = 21.727, b = 21.836, c = 5.133Å, Z = 4. The structure has been solved and refined to a final R of 0.068 for 1838 independent reflexions with I > 2σ(I). The peptide backbone is folded at the Leu residue (φ_L=?67.7,Ψ_L=?49.1°) without intramolecular hydrogen bonds. Considering each peptide plane, the Leu side-chain is oriented on the same side of that of the Phe residue and on the opposite side of that of the Met residue, respectively. The crystal conformation differs from all the other conformations proposed for FMLP-OMe and the anionic form of N-formyl-l -Met-l -Leu-l -Phe-OH (FMLP) in solution accounts for the amphiphilic character of the peptide, giving rise, through intermolecular hydrogen bonds, to a stacking of molecules which could be maintained in the aggregation states experimentally observed in solvents of low polarity. Intramolecular potential energy calculations have ben carried out in order to compare the energies of the various backbone conformers.     

Crystal structure and conformation of two N-tosyl-protected dipeptides containing amino acids with polar side-chains

X-Ray diffraction studies and energy-minimization calculations were carried out on two dipeptides, N-tosyl-l -Ser-Gly-OMe monohydrate (C₁₃H₁₈N₂O₆S·H₂O, compound A) and N-tosyl-l -Thr-Gly-OMe (C₁₄H₂₀N₂O₆, compound B). Compound A crystallized in the monoclinic system, space group P2₁ with unit cell parameters a= 4.915(1), b= 15.625(4), c= 11.003(1) Å, β= 91.28(1)°, V= 844.8 ų. M_r= 348.4, d= 1.37(2) g cm^?3, Z = 2, λ(Cu Kα) = 1.5418 Å, μ= 1.99 mm^?1, T=293 K. R= 0.032 for 1451 unique reflections with I > 2σ(I). Compound B crystallized in the orthorhombic system, space group P2₁2₁2₁, with unit cell parameters a= 5.050(2), b= 16.483(3), c= 20.769(5) Å, V= 1729.3 ų, Z = 4. M_r= 344.4, d= 1.32(2) g cm^?3, μ(Cu Kα)= 1.90 mm^?1. R= 0.040 for 1060 unique reflections with I > 2σ(I). The major difference in the backbone conformation of the two compounds is in their glycine residues, with the glycine residue in compound A adopting an extended conformation with φ= - 132.6(3)° and ψ= 175.3(3)° and that in compound B having a folded conformation with φ=?56.3(6)° and ψ=?42.6(7)°. In compound A the oxygen atom of the Ser side-chain and the carbonyl oxygen atom of glycine are bridged by the water of crystallization through O—H ··· O hydrogen bonds, resulting in the relatively rare trans conformation [χ=? 175.7(2)°] for this side-chain. The Thr side-chain in compound B is in the sterically preferred (tg^?) conformation [χ^1,1=? 179.4(4)° and χ^1,2=?62.3(5)°]. The conformations were found to be in general agreement with those obtained by an energy-minimization procedure. The energy-minimized structure of N-tosyl-l -Ser-Gly-Ome (anhydrous) showed a strong hydrophobic interaction between the methyl substituents of the tosyl group and the methyl ester (C—C = 4.08 Å).     

Conformational perturbations in retro-analogs of the tBuCO-Ala-Gly-NHiPr dipeptide Crystal structure of the retro-dipeptide with a reversed Ala-Gly amide bond

The three retro-analogs of the tBuCO-Ala-Gly-NHiPr dipeptide, in which each amide bond had been successively reversed, were studied in solution by ¹H-n.m.r. and i.r. spectroscopy with reference to the conformational properties of their parent dipeptide. Reversal of the Ala-Gly amide bond proved to perturb the folding tendency of the backbone less than the inversion of either of the terminal amide bonds. The crystal structure of the retro-peptide containing a reversed Ala-Gly amide bond was also solved by X-ray diffraction and constitutes the first available data for this retro-peptide series. In contrast to the βII-folded structure of the parent dipeptide, the retro-peptide molecule adopts an open conformation in the crystal.     

Structural variations in the crystal structures of two homologous DL-Leu and Δ-Leu containing peptides+

The similar conformations and interaction modes of Ac-DL-Leu-Nme₂ and Ac-Δ-Leu-NMe₂ molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the α,β-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to α,β-unsaturation, with a small shortening by 0.04 Å and 0.02 Å of the N-C^α and C^α-C′ bonds, respectively, and an increase by 6° of the N-C^α- C′ bond angle. The ethylenic and amide groups in the Δ-Leu derivative are far from coplanarity, and a significant electronic conjugation of the π-orbital is likely to be rejected.     

Crystal and molecular structure of l-valyl-l-lysine hydrochloride

l -Valyl-l -lysine hydrochloride, C₁₁N₃O₃H₂₃ HCl, crystallizes in the monoclinic space group P2, with a = 5.438(5), b = 14.188(5), c = 9.521(5) Å, β= 95.38(2)° and Z = 2. The crystal structure, solved by direct methods, refined to R = 0.036, using full matrix least-squares method. The peptide exists in a zwitterionic form, with the N atom of the lysine side-chain protonated. The two γ-carbons of the valine side-chain have positional disorder, giving rise to two conformations, χ¹¹₁= -67.3 and 65.9°, one of which (65.9°) is sterically less favourable and has been found to be less popular amongst residues branching at β-C. The lysine side-chain has the geometry of g^? tgt, not seen in crystal structures of the dipeptides reported so far. Interestingly, χ³₂ (63.6°) of lysine side-chain has a gauche⁺ conformation unlike in most of the other structures, where it is trans. The neighbouring peptide molecules are hydrogen bonded in a head-to-tail fashion, a rather uncommon interaction in lysine peptide structures. The structure shows considerable similarity with that of l -Lys-l -Val HO in conformational angles and H-bond interactions [4].     

Crystal structure and conformation of polypeptides: L-leucylglycylglycylglycine

Crystals of L-leucylglycylglycylglycine, LGGG (C₁₂H₂₂N₄O₅), grown from an ethanol-water solution, are orthorhombic, space groups P2₁2₁2₁, with unit cell dimensions (at 22 ± 3°) a = 9.337(1), b = 10.995(1), c = 15.235(1)Å, v = 1563.4 ų, Z = 4 with a density of D_obs= 1.29 g-cm^-3 and D_calc= 1.279 g°cm^-3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.029 for 1018 reflections with I ± 2s?. The molecule exists as a zwitterion in the crystal. The trans peptide backbone takes up a folded conformation at the middle glycylglycyl link accompanied by a significant nonplanarity up to Δω of 8° at the middle peptide and is relatively more extended at the two ends. The molecules are linked together intermolecularly in an infinite sequence of head to tail 1–4′ hydrogen bonds, as is typical of charged peptides. It is interesting to note that while glycylglycylglycine takes up an extended β-sheet conformation, addition of Leu to the N-terminal results in a bent conformation.     

柳珊瑚来源真菌Penicillium chrysogenum中聚酮-萜类化合物citrehybridonol及其单晶结构

目的 柳珊瑚来源真菌Penicillium chrysogenum中聚酮-萜类化合物citrehybridonol及其晶体结构和生物活性研究。方法 利用核磁、质谱等现代波谱分析方法和X-ray单晶衍射技术,对citrehybridonol的化学结构进行研究;运用细胞毒活性和抗菌活性模型对其生物活性进行评价。结果 citrehybridonol为首次获得其晶体,并首次对其单晶数据进行报道。生物活性测试结果表明,该化合物对测试的细菌菌株未显示抗菌活性,对肿瘤细胞株未见细胞毒活性。结论 citrehybridonol的单晶数据以及活性数据对今后系统研究聚酮-萜类化合物具有参考价值。     

Crystal structure and molecular conformation of achatin-I (H-Gly-d-Phe-Ala-Asp-OH), an endogenous neuropeptide containing a d-amino acid residue

In order to investigate the active conformation of achatin-I (H-Gly-d -Phe-Ala-Asp-OH), an endogenous neuropeptide from the Achatina fulica ganglia, its crystal structure and molecular conformation were analysed by the X-ray diffraction method. Crystals from methanol/dioxane are monoclinic, space group P2₁ with a=5.083(1), b= 9.125(1), c= 20.939(3) Å, β=94.73(1)° The structure was solved by direct methods and refined to R = 0.051 for 1714 independent reflections with Fo > σ(Fo). The molecule exists as a zwitterion with the Gly N-terminal end protonated and Asp β-carboxyl deprotonated; the C-terminal of Asp is in a neutral state. The molecule takes a kind of β turn structure with the d -Phe-Ala residues at the corner of the bend. This turn conformation is primarily formed by the strong intramolecular hydrogen bonds of NH(Gly)—O^δ1 (Asp) and NH(Asp)- O^δ1(Asp) pairs, thus forming a 15-membered ring structure. Judging from the published data concerning the structure-activity relationship, this turn conformation may reflect an important feature related to the neuroexcitatory activity of achatin-I.     

左氧氟沙星的单晶制备及其结构表征

目的培养左氧氟沙星单晶,进行结构表征。方法用乙腈–水体系培养单晶,并用单晶X射线衍射仪(SXRD)检测分析。结果制备得到左氧氟沙星无色片状晶体,该晶胞属于单斜晶系,空间群为P21,分子式为C18H20FN3O4·H2O,相对分子质量为379.38,晶体密度为1.469 mg/mm3,绝对构型为S构型。结论实验证明了左氧氟沙星的立体构型,培养的晶体晶型为一水合物。     

布南色林的单晶培养和结构确证

目的 培养布南色林的单晶,以验证所合成的化合物为布南色林.方法 通过温度、质量浓度、溶剂的考察,选择合适的条件,培养出大小适合X射线单晶衍射检测的布南色林单晶.结果 通过X射线单晶衍射测定,结果显示所得数据与文献报道一致,证明布南色林的化学结构正确.结论 采用本法可很好地获得大小适合X射线单晶衍射检测的布南色林单晶,并...