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1.
The crystal structure of the model tripeptide Boc-Aib-Gly-Leu-OMe ( 1 ) reveals two independent molecules in the asymmetric unit that adopt “enantiomeric” type I and type I′ β-turn conformations with the Aib and Gly residues occupying the corner (i + 1 and i + 2) positions. 13C cross polarization and magic angle sample spinning spectra in the solid state also support the coexistence of two conformational species. 13C-nmr in CDCl3 establishes the presence of a single species or rapid exchange between conformations. 400 MHz 1H-nmr provides evidence for conformational exchange involving a major and minor species, with β-turn conformations supported by the low solvent exposure of Leu(3) NH and the observation of NiH ↔ Ni+1H nuclear Overhauser effects. CD bands in the region 190–230 nm are positive, supporting a major population of type I′ β-turns. The isomeric peptide, Boc-Gly-Leu-Aib-OMe ( 2 ), adopts an “open” type II′ β-turn conformation in crystals. Solid state and solution nmr support population of a single conformational species. Chiral perturbation introduced outside the folded region of peptides may provide a means of modulating screw sense in achiral sequences. © 1998 John Wiley & Sons, Inc. Biopoly 45: 191–202, 1998  相似文献   

2.
The conformational analysis of a protected homodipeptide of 1-aminocyclopentanecarboxylic acid (Acc5) has been carried out. 1H-nmr studies establish a β-turn conformation for Boc-Acc5-Acc5-NHMe in chloroform and dimethylsulfoxide solutions involving the methylamide NH in an intramolecular hydrogen bond. Supportive evidence for the formation of an intramolecular hydrogen bond is obtained from ir studies. X-ray diffraction studies reveal a type III β-turn conformation in the solid state stabilized by a 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The ?,ψ values for both Acc5 residues are close to those expected for an ideal 310-helical conformation (?? ± 60°, ψ~ ±30°).  相似文献   

3.
For-Thp-Leu-ΔzPhe-OMe ( 2 ), an analogue of the chemotactic tripeptide For-Met-Leu-Phe-OMe, containing 4-aminotetrahydrothiopyran-4-carboxylic acid (Thp) and (Z)-2,3-didehydrophenylalanine (ΔzPhe) as achiral, conformationally restricted mimics of Met and Phe, respectively, has been synthesized. In the crystal the new formyltripeptide adopts a type I β-turn conformation stabilized by a weak H bond between the formylic oxygen and the ΔzPhe NH. 1H-nmr analysis based on NH solvent accessibility and nuclear Overhauser effect experiments suggests that the β-turn is not preferred in CDCl3 solution where a γ-turn, centered at the Thp residue, prevails. The biological activity of 2 has been determined on human neutrophils and compared to that of previously studied analogues. The tripeptide 2 is practically unable to elicit superoxide anion production and lysozyme release, while slight, but not statistically significant activity was induced in chemotaxis. The role of the orientation of the aromatic ring with respect to the backbone adjacent atoms is discussed. © 1994 John Wiley & Sons, Inc.  相似文献   

4.
The crystal state conformations of three peptides containing the α,α-dialkylated residues. α,α-di-n-propylglycine (Dpg) and α,α-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Alu-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II β-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: ? = 66.2°, ψ = 19.3°; III: ? = 66.5°. ψ = 21.1°) deviate appreciably from ideal values for the i + 2 residue in a type II β-turn. In both peptides the observed (N…O) distances between the Boc CO and Ala (3) NH groups are far too long (1: 3.44 Å: III: 3.63 Å) for an intramolecular 4 → 1 hydrogen bond. Boc-Ala-Dpg-Ata-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules HA and HB adopt consecutive β-turn (type III-III in HA and type III-I in IIB) or incipient 310-helical structures, stabilized by two intramolecular 4 → 1 hydrogen bonds. In all four molecules the bond angle N-Cα-C′ (τ) at the Dxg residues are ≥ 110°. The observation of conformational angles in the helical region of ?,ψ space at these residues is consistent with theoretical predictions. © 1995 John Wiley & Sons, Inc.  相似文献   

5.
Using a grid search technique, the entire conformational space of a system of four linked peptide units (tetrapeptide) was scanned to pick out geometrically possible 5→1 type hydrogen-bonded conformations defined as an α-turn. The energy minimization of these conformations led to 23 distinct minimum energy conformations (MECs) falling in 13 different classes. The presence of β and γ turn type hydrogen bonds along with 5→1 type hydrogen bond gave conformational variability in a given class. The occurrence of bifurcated hydrogen bonding network was a characteristic feature of most of the MECs. In many prototype MECs non-glycyl residues such as Ala and Pro could be accommodated. Comparison of MECs with the α-turn examples that are observed in proteins showed that the conformationally worked out MECs occurred in isolation in proteins, with the α-helical α-turn being distinctly the most predominant. © 1998 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   

6.
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°).  相似文献   

7.
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°, ψPro = 139.3°, ?Aib = 61.4°, and ψAib = 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.  相似文献   

8.
The solid state conformations of cyclo[Gly–Proψ[CH2S]Gly–D –Phe–Pro] and cyclo[Gly–Proψ[CH2–(S)–SO]Gly–D –Phe–Pro] have been characterized by X-ray diffraction analysis. Crystals of the sulfide trihydrate are orthorhombic, P212121, with a = 10.156(3) Å, b = 11.704(3) Å, c = 21.913(4) Å, and Z = 4. Crystals of the sulfoxide are monoclinic, P21, with a = 10.662(1) Å, b = 8.552(3) Å, c = 12.947(2) Å, β = 94.28(2), and Z = 2. Unlike their all-amide parent, which adopts an all-trans backbone conformation and a type II β-turn encompassing Gly-Pro-Gly-D -Phe, both of these peptides contain a cis Gly1-Pro2 bond and form a novel turn structure, i.e., a type II′ β-turn consisting of Gly–D –Phe–Pro–Gly. The turn structure in each of these peptides is stabilized by an intramolecular H bond between the carbonyl oxygen of Gly1 and the amide proton of D -Phe4. In the cyclic sulfoxide, the sulfinyl group is not involved in H bonding despite its strong potential as a hydrogen-bond acceptor. The crystal structure made it possible to establish the absolute configuration of the sulfinyl group in this peptide. The two crystal structures also helped identify a type II′ β-turn in the DMSO-d6 solution conformers of these peptides. © 1993 John Wiley & Sons, Inc.  相似文献   

9.
The molecular and crystal structures of one derivative and three homopeptides (from the di-to the tetrapeptide level) of the chiral, Cα, α-disubstituted glycine Cα-methyl, Cα-benzylglycine [(αMe)Phe], have been determined by x-ray diffraction. The derivative is mClAc-D -(αMe)Phe-OH, and the peptides are pBrBz-[D -(αMe)Phe]2-NHMe, pBrBz-[D -(αMe)Phe]3-OH hemihydrate, and pBrBz-[D -(αMe)Phe]4-OtBu sesquihydrate. All (αMe)Phe residues prefer ?,ψ torsion angles in the helical region of the conformational map. The dipeptide methylamide and the tripeptide carboxylic acid adopt a β-turn conformation with a 1 ← 4 C?O…?H? N intramolecular H bond. The structure of the tripeptide carboxylic acid is further stabilized by a 1 ← 4 C?O…?H? O intramolecular H bond, forming an “oxy-analogue” of a β-turn. The tetrapeptide ester is folded in a regular (incipient) 310-helix. In general, the relationship between (αMe)Phe chirality and helix screw sense is opposite to that exhibited by protein amino acids. A comparison is made with the conclusions extracted from published work on homopeptides from other Cα-methylated α-amino acids. © 1993 John Wiley & Sons, Inc.  相似文献   

10.
A tetrapetide containing an Aib residue, Boc-Asn-Aib-Thr-Aib-OMe, was synthesized as a peptide model for the N-glycosylation site in N-glycoproteins. Backbone conformation of the peptide and possible intramolecular interaction between the Asn and Thr side chains were elucidated by means of n.m.r. spectroscopy. Temperature dependence of NH proton chemical shift and NOE experiments showed that Boc-Asn-Aib-Thr-Aib-OMe has a tendency to form a β-turn structure with a hydrogen bond involving Thr and Aib4 NH groups. Incorporation of Aib residues in the peptide model promotes folding of the peptide backbone. With folded backbone conformation, carboxyamide protons of the Asn residue are not involved in hydrogen bond network, while the OH group of the Thr residue is a candidate for a hydrogen bond in DMSO-d6 solution.  相似文献   

11.
Conformations of the α-l -Rhap(1-2)-β-d -Glc1-OMe and β-d -Galp(1-3)-β-d -Glc1-OMe disaccharides and the branched title trisaccharide were examined in DMSO-d6 solution by 1H-nmr. The distance mapping procedure was based on rotating frame nuclear Overhauser effect (NOE) constraints involving C- and O-linked protons, and hydrogen-bond constraints manifested by the splitting of the OH nmr signals for partially deuteriated samples. An “isotopomer-selected NOE” method for the unequivocal identification of mutually hydrogen-bonded hydroxyl groups was suggested. The length of hydrogen bonds thus detected is considered the only one motionally nonaveraged nmr-derived constraint. Molecular mechanics and molecular dynamics methods were used to model the conformational properties of the studied oligosaccharides. Complex conformational search, relying on a regular Φ,Ψ-grid based scanning of the conformational space of the selected glycosidic linkage, combined with simultaneous modeling of different allowed orientations of the pendant groups and the third, neighboring sugar residue, has been carried out. Energy minimizations were performed for each member of the Φ,Ψ grid generated set of conformations. Conformational clustering has been done to group the minimized conformations into families with similar values of glycosidic torsion angles. Several stable syn and anti conformations were found for the 1→2 and 1→3 bonds in the studied disaccharides. Vicinal glycosylation affected strongly the occupancy of conformational states in both branches of the title trisaccharide. The preferred conformational family of the trisaccharide (with average Φ,Ψ values of 38°, 17° for the 1→2 and 48°, 1° for the 1→3 bond, respectively) was shown by nmr to be stabilized by intramolecular hydrogen bonding between the nonbonded Rha and Gal residues. © 1998 John Wiley & Sons, Inc. Biopoly 46: 417–432, 1998  相似文献   

12.
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) Å3. 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 ψT4=?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.  相似文献   

13.
In order to induce a β-turn conformation into the chemotactic linear tripeptide N-formyl-L -methionyl-L -leucyl-L -phenylalanine (fMLP), the new analogue N-formyl-L -methionyl-ΔZleucyl-L -phenylalanine methyl ester [ ΔZLeu]2f MLP-OMe ( 1 ) has been synthesized. The conformational and biochemical consequences of this chemical modification have been determined. Analogue 1 has been synthesized by using N-carboxy-(Z)-α,β-didehydroleucine anhydride as key compound to introduce the unsaturated residue at the central position of the tripeptide 1 . The x-ray analysis shows that 1 adopts in the crystal a type II β-turn conformation in which the new residue occupies the (i + 2) position, and an intramolecular H bond is formed between the formylic oxygen and the Phe NH. 1H-nmr analysis based on nuclear Overhauser effect measurements suggests that the same folded conformation is preferred in CDCl3 solution; this finding is also supported by molecular dynamics simulation. The biological activity of 1 has been determined on human neutrophils (polymorphonuclear leukocytes) and compared to that shown by f MLP-OMe. Chemotactic activity, granule enzyme release, and superoxide anion production have been determined. Analogue 1 is practically inactive as chemoattractant, highly active in the superoxide generation, and similar to the parent in the lysozyme release. The conformational restriction imposed on the backbone by the presence of the unsaturated residue is discussed in relation with the observed bioselectivity. © 1993 John Wiley & Sons, Inc.  相似文献   

14.
P A Raj  P Balaram 《Biopolymers》1985,24(7):1131-1146
The aggregation behavior of the chemotactic peptide analogs, Formyl-Met-Leu-Phe-OMe ( 1 ) and Formyl-Met-Aib-Phe-OMe ( 2 ), has been studied in chloroform and dimethylsulfoxide over the concentration range of 0.2–110 mM by 1H-nmr spectroscopy. Both peptides associate in CDCl3 at concentrations ≥ 2 mM, while there is no evidence for aggregation in (CD3)2SO. Analog 1 adopts an extended conformation in both solvents favoring association to form β-sheet structures. A folded, γ-turn conformation involving a 3 → 1 hydrogen bond between Met CO and Phe NH is supported by 1H-, 13C-nmr, and ir studies of analog 2 . The influence of backbone conformation on the ease of peptide aggregation is demonstrated by ir studies in CHCl3 and CD studies in dioxane.  相似文献   

15.
Protein β-turn classification remains an area of ongoing development in structural biology research. While the commonly used nomenclature defining type I, type II and type IV β-turns was introduced in the 1970s and 1980s, refinements of β-turn type definitions have been introduced as recently as 2019 by Dunbrack, Jr and co-workers who expanded the number of β-turn types to 18 (Shapovalov et al, PLOS Computat. Biol., 15, e1006844, 2019). Based on their analysis of 13 030 turns from 1074 ultrahigh resolution (≤1.2 Å) protein structures, they used a new clustering algorithm to expand the definitions used to classify protein β-turns and introduced a new nomenclature system. We recently encountered a specific problem when classifying β-turns in crystal structures of pentapeptide repeat proteins (PRPs) determined in our lab that are largely composed of β-turns that often lie close to, but just outside of, canonical β-turn regions. To address this problem, we devised a new scheme that merges the Klyne-Prelog stereochemistry nomenclature and definitions with the Ramachandran plot. The resulting Klyne-Prelog-modified Ramachandran plot scheme defines 1296 distinct potential β-turn classifications that cover all possible protein β-turn space with a nomenclature that indicates the stereochemistry of i + 1 and i + 2 backbone dihedral angles. The utility of the new classification scheme was illustrated by re-classification of the β-turns in all known protein structures in the PRP superfamily and further assessed using a database of 16 657 high-resolution protein structures (≤1.5 Å) from which 522 776 β-turns were identified and classified.  相似文献   

16.
A comparative study of four peptidomimetics of the sequence Phe-Met-Arg-Phe-amide (FMRFa) was performed to compare the conformational bias caused by trans-2,3-methanomethionine and α-methylmethionine stereoisomers. The specific compounds studied were F[(2S,3S)-cyclo-M] RFa, F[(2R,3R)-cyclo-M]RFa, F[(S)-α-MeM]RFa, and F[(R)-α-MeM]RFa. Molecular simulations based on CHARMm 22 indicate that γ-turn, inverse γ-turn, and α-helical conformations about the cyclo-M residue are accessible to the two F[cyclo-M]RFa stereoisomers. Similar calculations for F[(S)-α-MeM]RFa, and F[(R)-α-MeM]RFa indicate that the α-methylamino acids tend to favor α-helical conformations. The nmr data is presented for the four peptidomimetics. Most informative were the rotating frame nuclear Overhauser effect cross peaks between the NH protons proximal to the methionine surrogates, and the Cβ hydrogens. Overall, these nmr data indicate F[(2S,3S)-cyclo-M]RFa and F[(2R,3R)-cyclo-M]RFa preferentially adopt inverse γ-turn and γ-turn conformations, respectively, whereas F[(S)-α-MeM]RFa and F[(R)-α-MeM]RFa tend to form partial left- and right-handed helical structures (although energy differences between the two turn structures, and between the two helical structures are likely to be small). It is suggested that the wider NH-Cα-CO angle of cyclopropane amino acids and their more severe steric requirements around the Cβ carbons force the peptidomimetic N- and C-termini into the same region of conformational space. This favors C7 turns in the cyclopropane amino acid series relative to the less constrained α-methyl derivatives. © 1997 John Wiley & Sons, Inc. Biopoly 42: 439–453, 1997  相似文献   

17.
One chiral L ‐valine (L ‐Val) was inserted into the C‐terminal position of achiral peptide segments constructed from α‐aminoisobutyric acid (Aib) and α,β‐dehydrophenylalanine (ΔZPhe) residues. The IR, 1H NMR and CD spectra indicated that the dominant conformations of the pentapeptide Boc‐Aib‐ΔPhe‐(Aib)2‐L ‐Val‐NH‐Bn (3) and the hexapeptide Boc‐Aib‐ΔPhe‐(Aib)3‐L ‐Val‐NH‐Bn (4) in solution were both right‐handed (P) 310‐helical structures. X‐ray crystallographic analyses of 3 and 4 revealed that only a right‐handed (P) 310‐helical structure was present in their crystalline states. The conformation of 4 was also studied by molecular‐mechanics calculations. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   

18.
The influence of amino acids with contrasting conformational tendencies on the stereochemistry of oligopeptides has been investigated using an octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe, which contains two helix-promoting Aib residues and a central helix-destabilizing Gly-Gly segment. Single crystal x-ray diffraction studies reveal that a 3 10-helix is formed up to the penultimate Aib residue, at which point there is a helix reversal in the backbone, reminiscent of a C-terminal 6 → I hydrogen bond. The curious feature in the crystal is the solvation of the possible 6 → 1 bond by a CH3OH molecule, where the OH is inserted between O(3) and N(8) and participates in hydrogen bonds with both. The cell parameters are as follows: space group P212121, a = 10.649(4) Å, b = 15.694(5) Å, c = 30.181(8) Å, R = 6.7% for 3427 data (| F0| > 3σF) observed to 0.9 Å. Nuclear magnetic resonance studies in CDCl3 using NH group solvent accessibility and nuclear Overhauser effects as probes are consistent with a 3 10-helical conformation. In contrast, in (CD3)2SO, unfolding of the central segment results in a multiple β-turn structure, with β-turn conformations populated at residues 1–2, 3–4, and 6–7. CD studies in methanol-2,2,2-trifluoroethanol (TFE) mixtures also provide evidence for a solvent-dependent structural transition. Helical conformations are populated in TFE, while type II β-turn structures are favored in methanol. © 1996 John Wiley & Sons, Inc.  相似文献   

19.
The confortmational behavior of the cholecystokinin-related fragments CCK4, CCK5, and CCK6 as determined by 1H-nmr spectroscopy in DMSO-d6 and water and fluorescence-transfer measurements in aqueous medium are greatly dependent on the ionization states of these peptides. Under netral conditions, the backbones of CCK5 and CCK6 preferentially adopted folded forms with a β-turn including the four residues Gly-Trp-Met-Asp, probably stabilized by a hydrogen bond between the CO of Gly and the NH of Phe. In these structures, possible induced by an ionic interaction between the carboxylic group of Asp32 and the NH group of the N-terminal amino acid, the lateral chains of the various residues are quite distant from each other (15–16 Å). Under acidic conditions, extended structures without interactions between side chains predominate for CCK5 and CCK6, while for CCK4, a conformational change drawing the Trp and Phe side chains in close proximity was shown by fluorescence. The conformations observed in aqueous medium at physiological pH are discussed in relation to the biological activity of these peptides.  相似文献   

20.
We have synthesized and crystallized the cyclic peptide (Gly-Aib-Gly) 2. Its structure has been determined by conventional X-ray diffracti on methods. In the crystal it adopts a conformation with one β-turn (type I) and its mirror image at the other side of the ring. All conformation al angles are similar to those reported for these amino acid residues. In particular the Aib residue has a conformation intermediate between α- and 310-helical conformations. The ring is an adequate model for the β-turn conformation. A molecule of formic acid is found in the crystal which shows a very short hydrogen bond with one of the glycine carbonyl groups.  相似文献   

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