Design of peptides withα,β-dehydro-residues: synthesis,and crystal and molecular structure of a310-helical tetrapeptide Boc-l-Val-ΔPhe-ΔPhe-l-Ile-OCH3

Abstract: The peptide Boc-l -Val-ΔPhe-ΔPhe-l -Ile-OCH₃ was synthesized using the azlactone method in the solution phase, and its crystal and molecular structures were determined by X-ray diffraction. Single crystals were grown by slow evaporation from solution in methanol at 25°C. The crystals belong to an orthorhombic space group P2₁2₁2₁ with a = 12.882(7) Å, b = 15.430(5) Å, c = 18.330(5) Å and Z = 4. The structure was determined by direct methods and refined by a least-squares procedure to an R-value of 0.073. The peptide adopts a right-handed 3₁₀-helical conformation with backbone torsion angles: φ₁ = 56.0(6)°, ψ₁ = –38.0(6)°, φ₂ = –53.8(6)°, ψ₂ = 23.6(6)°, φ₃ = –82.9(6)°, ψ₃ = –10.6(7)°, φ₄ = 124.9(5)°. All the peptide bonds are trans. The conformation is stabilized by intramolecular 4→1 hydrogen bonds involving Boc carbonyl oxygen and NH of ΔPhe³ and CO of Val¹ and NH of Ile⁴. It is noteworthy that the two other chemically very similar peptides: Boc-Val-ΔPhe-ΔPhe-Ala-OCH₃ (i) and Boc-Val-ΔPhe-ΔPhe-Val-OCH₃ (ii) with differences only at the fourth position have been found to adopt folded conformations with two overlapping β-turns of types II and III′, respectively, whereas the present peptide adopts two overlapping β-turns of type III. Thus the introduction of Ile at fourth position in a sequence Val-ΔPhe-ΔPhe-X results in the formation of a 3₁₀-helix. The crystal structure is stabilized by intermolecular hydrogen bonds involving NH of Val¹ and carbonyl oxygen of a symmetry related (–x, y – 1/2, 1/2 + z) ΔPhe² and NH of ΔPhe² with carbonyl oxygen of a symmetry related (x, y1/2, 1/2 + z) Ile⁴. This gives rise to long columns of helical molecules linked head to tail running along [010] direction.     

Hydrogen bonding in peptide helices Analysis of two independent helices in the crystal structure of a peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe

The crystal structure determination of the heptapeptide Boc-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe reveals two peptide helices in the asymmetric unit. Crystal parameters are: space group P2₁, a =10.356(2) Å, b = 19.488(5) Å, c=23.756(6) Å, β= 102.25(2)°, V=4685.4ų, Z=4 and R = 5.7% for 7615 reflections [I>3σ(I)].Both molecules adopt largely α-helical conformations with variations at the C-terminus. Helix type is determined by analysing both 4 → 1 and 5 → 1 hydrogen-bond interactions and comparison with the results of analysis of protein structures. The presence of two 4 → 1 hydrogen-bond interactions, besides four 5→1 interactions in both the conformations provides an opportunity to characterize bifurcated hydrogen bonds at high resolution. Comparison of the two helical conformations with related peptide structures suggests that distortions at the C-terminus are more facile than at the N-terminus. © Munksgaard 1997.     

Cis/trans conformational equilibrium across the N‐methylphenylalanine2‐ N‐methylphenylalanine3 peptide bond of arginine vasopressin analogs

Abstract: Two cyclic analogs of vasopressin, ‐Pro‐Arg‐Gly‐NH₂ ( 1 ) and ‐Pro‐Arg‐Gly‐NH₂ ( 2 ) were synthesized by the solid phase method. Their structure was determined in aqueous solution by two‐dimensional NMR techniques and simulated annealing algorithm from an extended template in X‐PLOR. The total chemical shift correlation spectroscopy and rotating‐frame Overhauser enhancement spectroscopy of the peptides displayed four distinct sets of residual proton resonances. This suggests that both analogs adopt four families of conformations in H₂O/D₂O (9 : 1) (one major and three minor species). In further analysis only signals of major species (M) and of one minor species (m₁) were considered. The major species of both peptides include a trans peptide bond between the first and second residue, and a cis form between the second and third residue. In the minor species, all peptide bonds were found to exist in trans geometry.     

NMR conformational study of a model tetradecapeptide mimicking the RXVRG consensus cleavage site of a Xenopus luevis skin endoprotease

A model tetradecapeptide, used for the purification of the RXVRG-endoprotease from Xenopus laevis skin exudate, has been studied by two-dimensional NMR, correlation (COSY) and NOE (NOESY) spectroscopy. This peptide has the 5–9 consensus sequence (RXVRG), along with an acidic moiety (1–4) and a hydrophobic domain (10–14). Variations with temperature of NH chemical shifts in a dimethyl sulfoxide solution (low thermal coefficients at residues 6, 7 and 8) and quantified NOE values from four spectra at different mixing times clearly showed a structural organization in the consensus domain with φ-angles around [–40, –10°] for residues 7 and 8, and two NOE correlations of αH_iNH_i+2 type (5–7 and 6–8). Moreover, a privileged rotamer in the side chain is established for three residues (Val², Asp³ and Val⁷) and limited possibilities are discussed for seven others. Most of the folding trends were not observed in the [Ser⁷] derivative, underlying the relationship between the conformations and a full consensus sequence. In the model tetradecapeptide an equilibrium between two β-turns of type I, fragments 4–7 and 5–8, seems the most probable. Comparison between this tetradecapeptide and its 4–14 fragment, also a substrate for RXVRG-endoprotease, shows that the 1–3 moiety (DVD) influences the consensus domain structure(s) and clearly stabilizes the folded one(s). Finally, two analytical methods are developed in order to determine: (1) the trifluoroacetic acid content of the peptide samples, on the basis of ¹⁹F NMR spectroscopy; (2) the mean φ- and φ-angles of each residue, from the whole set of NH/αH coupling constants (³J_Nα) and NOE data at a local level. © Munksgaard 1995.     

Iminiumkohlensäurederivat-Salze, 7. Mitt. Teil I: Elektrophile Reaktionen von 2-Methylthio-5,6-dihydro-4H1,3-thiaziniumiodiden, 2-Methylthio-4,5-dihydrothiazoliumiodiden und 2-Methylthio-5-methylthiazoliumiodiden mit N-Nucleophilen

Iminium Carbonic Acid Derivative Salts VII, Part I: Electrophilic Reactions of 2-Methylthio-5,6-dihydro-4H-1,3-thiazinium Iodides, 2-Methylthio-4,5-dihydrothiazolium Iodides, and 2-Methylthio-5-methylthiazolium Iodides with N-Nucleophiles Cyclic salts of the dithiocarbonic acid diester imidium type ( 3, 5 ) react with NH₂-nucleophiles to the cyclic isothioureas 6 – 8 . Some of these compounds were oxidized to cyclic isothiourea-S,S-dioxides ( 9, 10 ).     

Cystine peptides.

NHCH₃ (X = Gly 1 , Ala 2 , Aib 3 , Leu 4 and D-Ala 5 ), have been investigated by Raman and circular dichroism (CD) spectroscopy. Solid state Raman spectra are consistent with β-turn conformations in all five peptides. These peptides exhibit similar conformations of the disulfide segment in the solid state with a characteristic disulfide stretching frequency at 519 ± 3 cm^-1, indicative of a trans-gauche-gauche arrangement about the C^α—C^β—S—S—C^β—C^α bonds. The results correlate well with the solid state conformations determined by X-ray diffraction for peptides 3 and 4. CD studies in chloroform and dimethylsulfoxide establish solvent dependent conformational changes for peptides 1, 3 and 5. Disulfide chirality has been derived using the quadrant rule. CD results together with previously reported nuclear magnetic resonance (n.m.r.) data suggest a conformational coupling between the peptide backbone and the disulfide segment.     

Circular dichroism and fluorescence spectroscopic analyses of a proline-rich glycoprotein from human parotid saliva

A proline-rich glycoprotein (PRG) was isolated from human parotid saliva and examined by circular dichroism and fluorescence spectroscopy. Addition of guanidine hydrochloride to PRG labeled with an extrinsic dansyl probe had no effect on the fluorescence spectra's 511 nm lambda-max location. Thermodynamic calculations supported the contention that PRG has no significant tertiary structure. Circular dichroism results for PRG were simulated by computer and a secondary structure composed of 70% random coil and 30%β-form conformation was predicted. Circular dichroism of PRG failed to detect either poly-L-proline type I or II structures. Deglycosylation of PRG had no measurable effect on the circular dichroism spectrum, indicating that the carbohydrate side chains had little influence on PRG secondary structure. Based upon mathematical calculations, β-turns were predicted around three glycosylated Asn residues of PRG. These collective data suggest that PRG is composed of a disordered polypeptide chain with at least three of the N-linked Asn residues participating in some type of β-turn.     

Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for the Management of Glioblastoma

Purpose

Localized chemotherapy has gained significant impetus for the management of malignant brain tumors. In the present study, we appraised the versatility of an in-situ gel forming self-assembling peptide, ac-(RADA)₄-CONH₂, as a biocompatible delivery depot of the chemotherapeutic drug doxorubicin (DOX) and the anticancer agent curcumin (CUR), respectively.

Methods

The morphology and mechanical properties of ac-(RADA)₄-CONH₂ were assessed with scanning electron microscopy (SEM) and rheological studies. The in vitro drug release from ac-(RADA)₄-CONH₂ was monitored in phosphate-buffered saline pH 7.4. Distribution of the fluorescent actives within the peptide matrix was visualized with confocal laser scanning microscopy (CLSM). The in vitro biological performance of the ac-(RADA)₄-CONH₂-DOX and ac-(RADA)₄-CONH₂-CUR was evaluated on the human glioblastoma U-87 MG cell line.

Results

SEM studies revealed that the ac-(RADA)₄-CONH₂ hydrogel contains an entangled nanofiber network. Rheology studies showed that the more hydrophobic CUR resulted in a stiffer hydrogel compared with ac-(RADA)₄-CONH₂ and ac-(RADA)₄-CONH₂-DOX, due to the interaction of CUR with the hydrophobic domains of the peptide nanofibers as confirmed by CLSM. In vitro release studies showed a complete DOX release from ac-(RADA)₄-CONH₂ within 4 days and a prolonged release for ac-(RADA)₄-CONH₂-CUR over 20 days. An increased cellular uptake and a higher cytotoxic effect were observed for ac-(RADA)₄-CONH₂-DOX, compared with DOX solution. Higher levels of early apoptosis were observed for the cells treated with the ac-(RADA)₄-CONH₂-CUR, compared to CUR solution.

Conclusions

The current findings highlight the potential utility of the in-situ depot forming ac-(RADA)₄-CONH₂ hydrogel for the local delivery of both water soluble and insoluble chemotherapeutic drugs.

     

α,ω-双-[对-甲氨基苯氧基]-戊烷及庚烷-N,N′-双取代衍生物的合成

α,ω-双-[对-氨基苯氧基]-烷类对感染日本血吸虫病的实驗动物具有显著疗效,惟毒性较大.本文叙述了α,ω-双-[对-甲氨基苯氧基]-戊烷及-庚烷-N,N′双取代衍生物的合成,希望这些衍生物的毒性减低,而疗效增大.n=5或7.R=-CH₂SO·ONa,-CH₂SO₂·ONa,-CH₂COONa, -CH₂CONH₂,-CH₂CN,-CONH₂,-COCH₃,-CH₂CONH₂,-COOC₂H₅.N,N′-双甲亚磺酸鈉及N,N′-双甲磺酸鈉衍生物系以α,ω-双-[对-甲氨基苯氧基]-戊烷Ⅰ及庚烷Ⅱ分別与烴甲亚磺酸鈉及烴甲磺酸鈉在碱性甲醇中作用生成.N,N′-双甲磺酸鈉衍生物与氰化鉀反应得N,N′-双乙腈衍生物,再行水解則得N,N′-双乙酸鈉衍生物.由对-N-氨基碳酰甲基-N-甲氨基苯酚、对-N-氨基碳酰-N-甲氨基苯酚,以及对-N-β-羥乙基-N-甲氨基苯酚分別与α,ω-二溴烷类縮合,得N,N′-双乙酰胺、N,N′-双碳酰胺、以及N,N′-双-β-羥乙基衍生物.N,N′-双碳酰胺亦由Ⅰ及Ⅱ直接与氰酸鉀反应制得。N,N′-双甲酸乙酯衍生物系以Ⅱ与氯代甲酸乙酯作用合成,而N,N′-双乙酰衍生物則按常法制取之。     

4-取代芬太尼类化合物的晶体结构和构效关系

以芬太尼为典型代表物的4-苯胺哌啶类化合物是一类具有独特结构类型、强度高、作用迅速的高效麻醉镇痛剂。该类化合物哌啶环的3位或4位引入适当取代基团能提高镇痛活性,其活性强度已达微克水平。芬太尼类化合物的构效关系研究表明:分子构象与生物活性之间关系密切。虽Peeters和Koch等人分别对芬太尼(R 4263)和4-甲氧甲基芬太尼类代表物(R 30490,R 30730)     

3-甲基芬太尼衍生物立体异构体的 QSAR 研究

用比较分子力场分析(CoMFA)方法研究了3-甲基芬太尼和羟甲芬太尼立体异构体的三维定量构效关系(3D-QSAR)。所得CoMFA-QSAR模型有很好的预测能力(γ²_{cros-validated}=0.716,n_{optimalcomponent}=5,γ²_conventional=0.999,s=0.052,F=1305.1),模型中,被研究化合物的构象可能就是其活性构象。以AM1方法进行量子化学计算,获得上述可能活性构象的结构参数及空间位置参数。基于这些参数,用偏最小二乘法(PLS)获得了被研究化合物的QSAR方程。所得PLS-QSAR模型具有较好的预测能力,并且显示被研究化合物的镇痛活性取决于分子中负电性的哌啶氮原子(N_PA)净电荷以及哌啶氮原子、羰基氧原子、1-β-苯环、4-N-苯环、3-甲基和2′-羟基的空间位置。     

Structure and conformation of peptides involving prolyl residue III. L-Prolyl-L-isoleucine monohydrate

The dipeptide, L-prolyl-L-isoleucine monohydrate (C₁₁ H₂₀N₂O₃· H₂O, molecular weight 246.3) crystallizes in the monoclinic space group P2₁, with a = 6.601(3)Å, b = 5.413(3) Å, c = 19.128(6) Å, β= 98.1(1)°, Z = 2, Do = 1.20g·cm^-3 and Dc = 1.208g·cm^-3. The structure was solved by MULTAN–80 and refined to a final R-factor of 0.081 for 594 reflections measured on a Enraf Nonius CAD-4 diffractometer. The peptide linkage exists in the trans conformation. The pyrrolidine ring is disordered with two alternate envelope conformations for the C^γ atom. The values of the sidechain torsion angles are: χ₁₁=– 63.6(17)°, χ₁₂= 171.1(16)° and χ₂=– 59.6(21)° for isoleucine (C-terminal). The crystal structure is stabilized by a three-dimensional network of N—H ? O, O—H ? O and C—H ? O hydrogen bonds. The dipeptide exists in the extended Conformation.     

Crystal and molecular structure of two geometrically restricted chemotactic tripeptides,analogues of formyl-methionine-leucine-phenylalanine*

The crystal structures of HCO-Met-Leu-Phe-OC(CH₃)₃, (CH₂₅H₃₉N₃O⁵S), fMLP-OtBu, and HCO-Metψ[CSNH]-Leu-Phe-OCH₃, (C₃₃H₃₃N₃O₄S₂), fM^SLP-OMe, have been determined by single crystal X-ray diffraction, and their conformational properties investigated by molecular mechanics energy calculations. Crystals of fMLP-OtBu are monoclinic, space group P2₁, a = 12.027(4), b = 9.492(3), c = 12.660(4) Å, β= 101.99(3)°, Z = 2; those of fM^SLP-OMe are orthorhombic, space group P2₁2₁2₁, a = 7.130(1), b = 12.097(2), c = 31.060(5) Å, Z = 4. The first compounds fMLP-OtBu is the t-butyl ester of the tripeptide fMLP that represents one of the most potent compounds in inducing the lysozyme release from human neutrophils that reflects the chemotactic activity. From the crystal structure, it is shown that the orientation of the phenylalanine side chain is largely affected by the presence of the bulky group. fM^SLP-OMe was shown to be inactive after thionation of the methionine residue in the original tripeptide. Nevertheless, the crystal structure does not reveal any influence of the presence of the thionated peptidic bond on the backbone conformation. The X-ray results have been used to generate parameters for empirical energy calculations. Subsequently, a strategy based on random generation of conformations followed by energy-minimization was applied to investigate the conformational space of thiopeptides, in comparison with normal peptides. From molecular free energy calculations, it is shown that the main influence of the introduction of a thioamide bond on the molecular structure is to prevent the existence of C⁷_eqconformations involving the thiomethionine residue. Consequently, a larger number of conformers are found to form intramolecular hydrogen bonds involving the formyl group, reducing its availability to interact with the receptor. For the first time, the theoretical prediction of the existence of C⁷_eq conformations for fMLP is made. The resulting conformers are compared to previously active structures of these chemotactic agents.     

The effect of conformation on the membrane permeation of coumarinic acid- and phenylpropionic acid-based cyclic prodrugs of opioid peptides

Abstract: In an earlier study using Caco-2 cells, an in vitro cell culture model of the intestinal mucosa, we have shown that the coumarinic-based ( 3 and 4 ) and the phenylpropionic acid-based ( 5 and 6 ) cyclic prodrugs were more able to permeate the cell monolayers than were the corresponding opioid peptides, [Leu⁵]-enkephalin ( 1 , H-Tyr-Gly-Gly-Phe-Leu-OH) and DADLE ( 2 , H-Tyr-D-Ala-Gly-Phe-D-Leu-OH). In an attempt to explain the increased permeation of the cyclic prodrugs, we have determined the possible conformations of these cyclic prodrugs in solution, using spectroscopic techniques (2D-NMR, CD) and molecular dynamics simulations. Spectroscopic as well as molecular dynamic studies indicate that cyclic prodrug 4 exhibits two major conformers (A and B ) in solution. Conformer A exhibited a type I β-turn at Tyr1-D-Ala2-Gly3-Phe4. The presence of a turn was supported by ROE cross-peaks between the NH of D-Ala2 and the NH of Gly3 and between the NH of Gly3 and the NH of Phe4. Conformer B of cyclic prodrug 4 consisted of type II β-turns at the same positions. The type II turn was stabilized by hydrogen bonding, thus forming a more compact structure, whereas the type I turn did not exhibit similar intramolecular hydrogen bonding. Spectroscopic data for compounds 3, 5 and 6 are consistent with the conclusion that these cyclic prodrugs have solution structures similar to those observed with cyclic prodrug 4 . The increased lipophilicity and well-defined secondary structures in cyclic prodrugs 3 – 6 , but not in the linear peptides 1 and 2, could both contribute to the enhanced ability of these prodrugs to permeate membranes.     

Spontaneous and oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates

Methamidophos (CH₃O(NH₂)P(O)SCH₃) and phosphoramidates, with the general structure RO(NH₂)P(O)OC₆H₄-p-NO₂, in which R = C₂H₅, ClCH₂CH₂, FCH₂CH₂ and F₃CCH₂, as well as (NH₂)₂P(O)OC₂H₄-p-NO₂ were synthesized to investigate the relationship between the rates of inhibition and of spontaneous reactivation of AChE inhibited by these organophosphates and their potential as prophylactics against nerve agent poisoning. The phosphoramidates inhibit electric eel acetylcholinesterase (EEAChE), the bimolecular inhibition rate constants ranging from 5×l0⁴ to 3×l0⁶ M^–1·min^–1 at pH 7.5, 25° C. The inhibited enzymes reactivate spontaneously, with half-lives ranging from 1.3 to 15 h at pH 7.5, 25° C. These half-lives increase 2–4 fold when the temperature is raised to 37° C. Reactivation is accelerated by micromolar concentrations of oximes such as obidoxime and HI-6. Aging of the inhibited enzymes was not observed. Nevertheless, reactivation appears to be incomplete for some of the inhibited enzymes. The title compounds seem promising as prophylactic agents against nerve agent intoxication.     

Conformational analysis of μ-selective [D-Ala2,MePhe4]enkephalins

The conformational space of the potent μ-selective opioids [D-Ala²,MePhe⁴,Gly-o1⁵]enkephalin (DAGO) and [D-Ala²,MePhe⁴,Gly-o1⁵]enkephalin (FK 33-824) has been analyzed by ¹H-NMR spectroscopy and theoretical calculations involving systematic conformational searching and energy minimizations. A cis-trans equilibrium of the Gly³-MePhe⁴ amide bond is induced by the N-methyl group, and the more energetically favoured trans isomer is proposed as the biologically relevant form. A compact interaction between the side chains of Tyr¹ and D-Ala² was demonstrated by NOE and ROE effects in both peptides in D₂O and DMSO-d₆, further supported by shielding of the D-Ala² methyl protons in both solvents. Analysis of coupling constants, NOE and ROE data indicated significant restriction of the conformational freedom of the MePhe⁴ side-chain for both peptides in the two solvents. The NMR results and theoretical calculations point towards folded low energy conformations characterized by a β₁₁-type turn around Gly³-MePhe⁴. For the trans isomer, a Tyr¹-MePhe⁴ phenyl ring separation between 8.5 and 12.5 Å was accompanied by proximity between the D-Ala² side chain and the C-terminal in low energy conformations The results are in good agreement with available data on related active enkephalins. The conformational effects induced by simultaneous incorporation of D-Ala² and MePhe⁴ in enkephalins is discussed in the light of the enhanced μ-opioid receptor selectivity and activity of these peptides.     

Molecular structures of two crystalline forms of the cyclic heptapeptide antibiotic ternatin,cyclo[-β-OH-d-Leu-d–Ile–(NMe)Ala (NMe)Leu-Leu-(NMe)Ala-d–(NMe)Ala-]

The crystal structures of two solvated forms of ternatin, cyclo[-β-OH-d -Leu-d -Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-d -(NMe)Ala-] are reported. The first crystallizes with two molecules of peptide and one of dioxane in the asymmetric unit: P2₁2₁2₁, a = 11.563(1), b = 21.863(2), c = 36.330(4) Å. The second crystallizes with two molecules of peptide and one of water in the asymmetric unit: P2₁2₁2₁, a = 14.067(2), b = 16.695(1), c = 36.824(6) Å. N-Methylation of four of the seven residues of ternatin appears to reduce the number of low-energy conformations the molecule can assume. The same H-bonded macrocyclic ring conformation is adopted by the backbone of each of the four molecules observed here. All the amino-acid side chains, with the exception of d -Ile², have similar orientations in each of the four conformers. The heptapeptide macrocycle is characterized by: (i) a cis peptide between (NMe)Ala³ and (NMe)Leu⁴, (ii) a type II β-bend, involving residues Leu⁵-(NMe)Ala⁶-d -(NMe)Ala⁷-β-OH-d -Leu², stabilized by two H-bonds, N1′05 and N5′01, between Leu⁵ and β-OH-d -Leu¹ residues, (iii) a third intramolecular H-bond, observed in each of the four molecules, between the hydroxyl group of β-OH-d -Leu¹ and the carbonyl oxygen of d -Ile².     

Fluorogenic substrates for chymotrypsin with new fluorescent markers

Several substrates for chymotrypsin Glt-Phe-NHR_x have been synthesized, where R_xNH₂ are the compounds 3-aminocoumarin (2), 6-aminocoumarin (3), 3-acetamido-6-aminocoumarin (4), 3-acetamido-8-aminocoumarin (5), 7-amino-4-methyl-2-quinolinone (AMQ), (6). The fluorescence properties of the new substrates and those of the corresponding free amines were examined. The compound 7-glutarylphenylalaninamido-4-methyl-2-quinolinone (Glt-Phe-AMQ), (15), provided a new suitable substrate for chymotrypsin determination. The enzymatic release of the fluorophore AMQ was measured at Λex = 360nm and Λem=435nm. The Km of 15 was 0.5mM and its kcat/Km ratio was 47 M^-1 s^-1. By using this substrate, the detection limit of chymotrypsin was 10 ng/ml.     

Linear tripeptide conformation

The structures of two tripeptides, Cbz-glycylglycyltyrosine methyl ester (ZGGYOMe) and Cbz-glycyl-(D,L)tyrosylglycine ethyl ester (ZGYGOEt) have been determined from single-crystal X-ray diffraction data. Crystals of ZGGYOMe are monoclinic, space group P2₁, with a= 12.427(3), b= 4.999(3), c= 17.401(6) Å, β= 99.98(2)° and Z= 2. The final R-index is 0.049 for 1698 reflections with I≥2 σ(I). Crystals of ZGYGOEt are monoclinic, space group P2₁/n with a= 12.134(8), b= 14.614(3), c= 26.154(9) Å, β= 98.78(4)°, Z= 8. The final R-index is 0.067 for 4457 reflections with I≥2 σ(I). Both peptides adopt highly extended structures; principal torsion angles are ω₀= 175.0(4)°, φ₁= 69.2(5)°, ψ₁=? 154.9(4)°, ω₁=?175.8(4)°, φ₂= 165.4(4)°, ψ₂= 154.2(3)°, ω₂= 169.6(3)°, φ₃=?94.8(5)°, ψ₃=?47.6(5)° for ZGGYOMe and, for the two independent molecules of ZGYGOEt, ω₀= 177.9(4)°, 178.9(4)°, φ₁=?172.0(4)°, 169.7(4)°ψ₁= 174.4(4)°, ?162.5(4)°; ω₁= -170.1(4)°, 176.7(4)°; φ₂=?130.8(4)°, 130.3(5)°; ψ₂= 162.8(4)°, ?163.3(4)°; ω₂=?177.6(4)°, 176.2(4)°; φ₃=? 169.9(4)°, 172.9(4)°; ψ₃=? 168.2(4)°, 160.9(4)°. The structures are of interest since the first one adopts a conformation unlike those of related GGX sequences and the latter shows an antiparallel hydrogen-bonding pattern.     

Structure and conformation of linear peptides XIII. Structure of l-phenylalanyl-glycyl-glycine

The crystal structure of a tripeptide, l -phenylalanyl-glycyl-glycine (C₁₃H₁₇,N₃O₄), molecular weight = 279.3, has been determined. The crystals are orthorhombic, space group P 2₁2₁2₁, with a= 5.462(1) A, b= 15.285(5), c= 16.056(4), Z = 4 , and P(calc) = 1.384 g. cm^-3. The final R-index is 0.052 for 866 reflections with θ/λ≤ 0.55 A^-1 and 1 > σ. The molecule exists as a zwitterion, with the N-terminus protonated and the C-terminus in an ionized form. Both the peptide units are in the trans configuration and planar, though one of them shows significant deviations from planarity (|Δ| = 5.1°). The peptide backbone is folded, with the torsion angles of ψ₁= 116.2(5)°, ψ₃₁= 178.8(4), φ₂=?89.7(5), ψ₂=?28.9(6), ω₂=?174.9(4), φ₃= 134.9(5), ψ₃₁= 7.8(6), ψ₃₂=?172.6(4). The terminal glycine adopts a “d -residue” conformation. For the sidechain of phenylalanine, χ₁= 175.5(4), χ₂= - 127.0(6).