β-Turn conformations in crystal structures of model peptides containing α,α-Di-n-propylglycine and α,α-Di-n-butylglycine

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-C^α-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.     

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.     

α,β-Dehydro-amino acid residues in the design of peptide structures: Synthesis,crystal structure,and molecular conformation of two homologous peptides—N-Ac-Dehydro-Phe-L-Leu-OCH3 and N-Ac-Dehydro-Phe-NorVal-OCH3

The dehydro-residue containing peptides N-Ac-dehydro-Phe-L -Leu-OCH₃ ( I ) and N-Ac-dehydro-Phe-NorVal-OCH₃ ( II ) were synthesized by the usual workup procedures. The peptides crystallize from their solutions in methanol in space group P6₅: ( I ) a = b = 12.528(2) Å, c = 21.653(5) Å; ( II ) a = b = 12.532(2) Å, c = 21.695(4) Å. The structures were determined by direct methods. Both peptides adopt similar conformations with ?,ψ of dehydro-Phe as follows: ( I ) ?57.0(5)° and ?37.0(5)°; ( II ) ?56.0(5),° and ?37.5(5)°. The observed data on dehydro-Phe when placed at the (i + 1) position show that the ?,ψ values of dehydro-Phe are either ?60°, 140° or ?60°, ?30°. The conformation of ?60°, 140° can be accommodated only with a flexible residue at the (i + 2) position while the ?,ψ values of ?60°, ?30° are obtained with a bulky residue at the (i + 2) position as in the present structures. The molecules are packed in a helical way along the c axis. These are held by two strong intermolecular hydrogen bonds involving both NH as donors and acetyl group and dehydro-Phe oxygen atoms as acceptors. © 1994 John Wiley & Sons, Inc.     

Crystal structure of the collagen model peptide (Pro‐Pro‐Gly)4‐Hyp‐Asp‐Gly‐(Pro‐Pro‐Gly)4 at 1.0 Å resolution

The single‐crystal structure of the collagen‐like peptide (Pro‐Pro‐Gly)₄‐Hyp‐Asp‐Gly‐(Pro‐Pro‐Gly)₄, was analyzed at 1.02 Å resolution. The overall average helical twist (θ = 49.6°) suggests that this peptide adopts a 7/2 triple‐helical structure and that its conformation is very similar to that of (Gly‐Pro‐Hyp)₉, which has the typical repeating sequence in collagen. High‐resolution studies on other collagen‐like peptides have shown that imino acid‐rich sequences preferentially adopt a 7/2 triple‐helical structure (θ = 51.4°), whereas imino acid‐lean sequences adopt relaxed conformations (θ < 51.4°). The guest Gly‐Hyp‐Asp sequence in the present peptide, however, has a large helical twist (θ = 61.1°), whereas that of the host Pro‐Pro‐Gly sequence is small (θ = 46.7°), indicating that the relationship between the helical conformation and the amino acid sequence of such peptides is complex. In the present structure, a strong intermolecular hydrogen bond between two Asp residues on the A and B strands might induce the large helical twist of the guest sequence; this is compensated by a reduced helical twist in the host, so that an overall 7/2‐helical symmetry is maintained. The Asp residue in the C strand might interact electrostatically with the N‐terminus of an adjacent molecule, causing axial displacement, reminiscent of the D‐staggered structure in fibrous collagens. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 436–447, 2013.     

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.     

Peptide design: Crystal structure of a helical peptide module attached to a potentially nonhelical amino terminal segment

The peptide Boc-Gly-Dpg-Gly-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been designed to examine the structural consequences of placing a short segment with a low helix propensity at the amino terminus of a helical heptapeptide module. The Gly-Dpg-Gly segment is a potential connecting element in the synthetic construction of a helix-linker-helix motif. Crystal parameters for the peptide are P2₁, a = 8.651(3) Å, b = 46.826(13) Å, c = 16.245 Å, β = 90.13(3)*, Z = 4; 2 independent molecules/asymmetric unit. The structure reveals almost identical conformations for the two independent molecules. The backbone is completely helical for residues 2–9, with one 4 → 1 hydrogen bond and six 5 → 1 hydrogen bonds. The α,α-di-n-propylglycine residue adopts a helical conformation. Gly(1) adopts an extended conformation resulting in a nonhelical N-terminus, with the Boc group swinging away from the helix. The lateral association of helices in the b axis direction is unusual in that the helix axes are directed up or down (parallel or antiparallel) by pairs: ↓↓↑↑↓↓, etc. © 1996 John Wiley & Sons, Inc.     

Conformational Preferences of Heterochiral Peptides. Crystal Structures of Heterochiral Peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala-OMe-Enhanced Stability of β-sheet Through C-H…O Hydrogen Bonds

Abstract

The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala-Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group P2₁2₁2₁ with a = 9.401 (4), b = 17.253 (5), c = 36.276 (9)Å, V = 5884 (3) ų, Z = 8, R = 0.086. VALa crystallises in space group P2₁ with a = 9.683 (9), b = 17.355 (7), c = 18.187 (9) Å, β = 95.84 (8)°, V = 3040(4) ų, Z = 4, R = 0.125. There are two molecules in the asymmetric unit in antiparallel β-sheet arrangement in both the structures. Several of the C^α hydrogens are in hydrogen bonding contact with the carbonyl oxygen in the adjacent strand.

An analysis of the observed conformational feature of D-chiral amino acid residues in oligopeptides, using coordinates of 123 crystal structures selected from the 1998 release of CSD has been carried out. This shows that all the residues except D-isoleucine prefer both extended and α_L conformation though the frequence of occurence may not be equal. In addition to this, D-leucine, valine, proline and phenylalanine have assumed α_R conformations in solid state. D-leucine has a strong preference for helical conformation in linear peptides whereas they prefer an extended conformation in cyclic peptides.     

Structure of guanylyl-3',5'-cytidine monophosphate. II. Description of the molecular and crystal structure of the calcium derivative in space group P2(1).

The structural features of calcium guanosine-3′,5′-cytidine monophosphate (GpC) have been elucidated by X-ray diffraction analysis. The molecule was crystallized in space group P2₁ with cell constants of a = 21.224 Å, b = 34.207 Å, c = 9.327 Å, and β = 90.527°, Z = 8. The hydration of the crystal is 21% by weight with 72 water molecules in the unit cell. The four GpC molecules in the asymmetric unit occur as two Watson-Crick hydrogen-bonded dimers related by a pseudo-C face centering. Each dimer consists of two independent GpC molecules whose bases are hydrogen bonded to each other in the traditional Watson-Crick fashion. Each dimer possesses a pseudo twofold axis broken by a calcium ion and associated solvent. The four molecules are conformationally similar to helical RNA, but are not identical to it or to each other. Instead, values of conformational angles reflect the intrinsic flexibility of the molecule within the range of basic helical conformations. All eight bases are anti, sugars are all C3′-endo, and the C4′-C5′ bond rotations are gauche-gauche. The R factor is 12.6% for 2918 observed reflections at 1.2-Å resolution.     

Unfolding of an α-helix in peptide crystals by solvation: Conformational fragility in a heptapeptide

The structure of the peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been determined in crystals obtained from a dimethylsulfoxide–isopropanol mixture. Crystal parameters are as follows: C₃₈H₆₉N₇O₁₀ · H₂O · 2C₃H₇OH, space group P2₁, a = 10.350 (2) Å, b = 26.084 (4) Å, c = 10.395(2) Å, β = 96.87(12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 σ (F). A single 5 → 1 hydrogen bond is observed at the N-terminus, while two 4 → 1 hydrogen bonds characteristic of a 3₁₀-helix are seen in the central segment. The C-terminus residues, Ala(6) and Leu(7) are expended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C-terminal segment, while a water molecule interacts with the N-terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol-water [ I. L. Karle, J. L. Flippen-Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62–73] in which two independent molecules reveal an almost perfect α-helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDC1₃ and (CD₃)₂SO. A helical conformation is supported in the apolar solvent CDCl₃, whereas almost complete unfolding is observed in the strongly solvating medium (CD₃)₂SO. © 1993 John Wiley & Sons, Inc.     

Helical segment analysis of α-helical regions in proteins

The methods suggested earlier for the analysis and representation of protein structural data are now extended to the helical regions in finer details. These enable better handling of characterization of bends and distortions, for which statistical parameters are also developed. Using latest myoglobin data, best experimental parameters for the α-helix are deduced to be r_N = 1.55 (0.13) Å, r = 2.28 (0.12) Å, r_C′ = 1.70 (0.10) Å, r₀ = 2.02 (0.12) Å, ? = 100.5 (2.3)°, and t = 1.495 (0.055) Å.     

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.     

Crystal structure,conformational analysis,and molecular dynamics of tetra-O-methyl-(+) -catechin

The structure of tetra-O-methyl- (+) -catechin has been determined in the crystalline state. Two independent molecules, denoted structure A and structure B, exist in the unit cell. Crystals are triclinic, space group P1, a = 4.8125(2) Å, b = 12.9148(8) Å, c = 13.8862(11) Å, α = 86.962(6) °, β = 89.120(5)°, γ = 88.044(5)°, Z = 2, D_c = 1.336 g cm^?3, R = 0.033 for 6830 observations. The heterocyclic rings of the crystal structures are compared to previous results for 8-bromotetra-O-methyl-(+)-catechin, penta-O-acetyl-(+)-catechin, and (?) -epicatechin. One of the two molecules has a heterocyclic ring conformation similar to that observed previously for (?)-epicatechin, and the other has a heterocyclic ring conformation similar to one predicted earlier in a theoretical analysis of dimers of (+)-catechin and (?) -epicatechin. Both structure A and structure B in the crystal have heterocyclic ring conformations that place the dimethoxyphenyl substituent at C(2) in the equatorial position. However, this heterocyclic ring conformation does not explain the proton nmr coupling constant measured in solution. Molecular dynamics simulations show an equatorial ? axial interconversion of the heterocyclic ring, which can explain the nmr results. © 1993 John Wiley & Sons, Inc.     

Theoretical Study of the Conformations of Pustulan [(1⇒6)-β-D)-Glucan]

Abstract

The total potential energy including nonbondedJuntorsional and hydrogen bond contributions has been computed for pustulan, a (1?6) linked β-D-glucan polysaccharide, as a function of rotational angles φ, ψ, and ω The (φ, ψ, ω)-space contains many local minima and at least three distinct deep minima. Two minima at (φ, ψ, ω)=(25°,190°,gg) and (φ, ψ, ω)=(65°,150°,gg) of almost equal energies have helical parameters (n=5.2, A=1.0Å) and (n=3.2, h= 1.5Å), respectively. A third minimum at (φ, ψ, ω)=(40°,70°gt) leads to an extended zig-zag structure (n=2.2, h=2.2Å). Energy maps obtained for gentiobiose, the disaccharide of pustulan, also reveal many local minima and the small energy differences among them indicate that gentiobiose is extremely flexible. Gentiodextrins, a family of cyclic molecules of (l?6)-β-D- glucose residues, were also studied. Conformations free from steric hindrance were found for cyclic molecules with three to six glucose residues.     

Crystal structure and a twisted β-sheet conformation of the tripeptide L-leucyl-L-leucyl-L-leucine monohydrate trimethanol solvate: Conformation analysis of tripeptides

In order to test the helical preference of short oligo-L -leucines, we crystallized the tripeptide L -leucyl-L .-leucyl-L -leucine (LLL) and carried out x-ray diffraction studies of it (L -leucyl-L -leucyl-L leucine)₂. 3CH₃OH. H₂O, (C₃₉H₈₄N₆O₁₂). Crystallized in the monoclinic system, space group P2₁, cell parameters: a = 12.031(2), b = 15.578(3), c = 14.087(2) Å, α = 90°, β = 97.29(1)°, γ = 90°, V = 2618.6 ų. MW = 829.1, D_c = 1.051 gcm^?3. R index of 0.057 for 4213 reflections (λ_cukα = 1.5418 Å) > 2σ. LLL takes tip the β-sheet rather than a helical conformation in the crystalline stale. The three methanol molecules and the water molecule that constitute the solvent of crystallization form a network of hydrogen bonds to the LLL molecules and to one another. It is rather remarkable that though A and L have stronger helical preferences than G, neither AAA nor LLL form the crystalline helix but GAL does, indicating that the helical preferences depend on the sequence context. The residue L2 in molecule A and the residues L1 and L3 of molecule B do not show the preferred conformation for forming helices. Further, very remarkably. LLL exhibits a unique super secondary feature of the protein folding topology, namely the twisted β-sheet. Where as most short peptides show only the classical p-sheet conformation. Thai even the tripeptide LLL is able to exhibit the twisted β-sheet conformation, and with the correct left-handed twist this suggests that even very short peptide segments possess the ability to assume several of the characteristic topological features exhibited by proteins. An extensive review of tripeptide conformations has been carried out and some results of this study have been included here. © 1995 John Wiley & Sons, Inc.     

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.     

Stereochemistry of Schellman motifs in peptides: Crystal structure of a hexapeptide with a C‐terminus 6 → 1 hydrogen bond

The Schellman motif is a widely observed helix terminating structural motif in proteins, which is generated when the C‐terminus residue adopts a left‐handed helical (α_L) conformation. The resulting hydrogen‐bonding pattern involves the formation of an intramolecular 6 → 1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the sequence. Thus far, the Schellman motif has been characterized crystallographically only in peptide helices of length 7 residues or greater. The structure of the hexapeptide Boc–Pro–Aib–Gly–Leu–Aib–Leu–OMe in crystals reveal a short helical stretch terminated by a Schellman motif, with the formation of 6 → 1 C‐terminus hydrogen bond. The crystals are in the space group P2₁2₁2₁ with a = 18.155(3) Å, b = 18.864(8) Å, c = 11.834(4) Å, and Z = 4 . The final R₁ and wR₂ values are 7.68 and 14.6%, respectively , for 1524 observed reflections [F_o ≥ 3ς(F_o)]. A 6 → 1 hydrogen bond between Pro(1)CO · · · Leu(6)NH and a 5 → 2 hydrogen bond between Aib(2)CO · · · Aib(5)NH are observed. An analysis of the available oligopeptides having an achiral Aib residue at the penultimate position suggests that chain length and sequence effects may be the other determining factors in formation of Schellman motifs. © 1999 John Wiley & Sons, Inc. Biopoly 50: 13–22, 1999     

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.     

Conformational variability of Gly-Gly segments in peptides: A comparison of the crystal structures of an acyclic pentapeptide and an octapeptide

The crystal structure of an acyclic pentapeptide, Boc-Gly-Gly-Leu-Aib-Val-OMe, reveals an extended conformation for the Gly-Gly segment, in contrast to the helical conformation determined earlier in the octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe [I. L. Karle, A. Banerjee, S. Bhattacharjya, and P. Balaram [1996] Biopolymers, Vol. 38, pp. 515–526). The pentapeptide crystallizes in space group P2₁ with one molecule in the asymmetric unit. The cell parameters are: a = 10.979(2) Å, b = 9.625(2) Å, c = 14.141(2) Å, and β = 96.93(1)°, R = 6.7% for 2501 reflections (I > 3σ(I)). The Gly-Gly segment is extended (ϕ₁ = −92°, ψ₁ = −133°, ϕ₂ = 140°, ψ₂ = 170°), while the Leu-Aib segment adopts a type II β-turn conformation (ϕ₃ = −61°, ψ₃ = 130°, ϕ₄ = 71°, ψ₄ = 6°). The observed conformation for the pentapeptide permits rationalization of a structural transition observed for the octapeptide in solution. An analysis of Gly-Gly segments in peptide crystal structures shows a preference for either β-turn or extended conformations. © 1997 John Wiley & Sons, Inc.     

X-Ray Studies on Crystalline Complexes Involving Amino Acids and Peptides XXXI. Effect of Chirality on Ionization State,Stoichiometry and Aggregation in the Complexes of Oxalic Acid with L-and DL-histidine

Abstract

Crystals of the oxalic acid complex of L-histidine (orthorhombic P2₁2₁2₁; a=5.535(4), b=6.809(4), c=26.878(3) Å) R= 3.6% for 1188 observed reflections) contain histidine molecules and semi-oxalate ions in the 1:1 ratio, while the ratio is 1:2 in the crystals of the DL-histidine complex (monoclinic P2₁ lc; a=6.750(7), b=10.139(2), c=19.352(2) Å, β= 90.8°; R= 3.7% for 3176 observed reflections). The histidine molecule in the latter has an unusual ionization state with positively charged amino and imidazole groups and a neutral carboxyl group. The molecule has the sterically least favourable allowed conformation with the side chain imidazole ring staggered between the α-amino and the α- carboxyl (carboxylate) groups, in both the structures. The unlike molecules aggregate into separate alternating layers in both of them. There are elements of similarity in the aggregation patterns in the semi-oxalate layers in the two complexes, but the patterns in the amino acid layers are entirely different. Interestingly, the crystal structure of L-histidine semi-oxalate has broad similarities with that of DL-histidine glycolate, demonstrating how broad features of aggregation could be retained inspite of changes in chirality and composition. The unusual ionization state of the amino acid molecule in the DL-histidine complex is reflected in a hitherto unobserved aggregation pattern in its crystal structure.     

Role of two consecutive α,β-dehydrophenylalanines in peptide structure: Crystal and molecular structure of Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe

An N^α-protected model pentapeptide containing two consecutive ΔPhe residues, Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe, has been synthesized by solution methods and fully characterized. ¹H-nmr studies provided evidence for the occurrence of a significant population of a conformer having three consecutive, intramolecularly H-bonded β-bends in solution. The solid state structure has been determined by x-ray diffraction methods. The crystals grown from aqueous methanol are orthorhombic, space group P2₁2₁2₁, a = 11.503(2), b = 16.554(2), c = 22.107(3) Å, V = 4209(1) Å,³ and Z = 4. The x-ray data were collected on a CAD4 diffractometer using CuK_a radiation (λ = 1.5418 Å). The structure was determined using direct methods and refined by full-matrix least-squares procedure. The R factor is 5.3%. The molecule is characterized by a right handed 3₁₀-helical conformation (〈ϕ〉 = −68.2°, 〈ψ〉 = −26.3°), which is made up of two consecutive type III β-bends and one type I β-bend. In the solid state the helical molecules are aligned head-to-tail, thus forming long rod like structures. A comparison with other peptide structures containing consecutive ΔPhe residues is also provided. The present study confirms that the -ΔPhe-ΔPhe-sequence can be accommodated in helical structures. © 1997 John Wiley & Sons, Inc. Biopoly 42: 373–382, 1997