Observation of a mixed antiparallel and parallel β-sheet motif in the crystal structure of Boc-Ala-Ile-Aib-OMe

A diastereomeric mixture of the tripeptide Boc-Ala-Ile-Aib-OMe crystallized in the space group Pl from CH₃OH/H₂O. The unit cell parameters are a= 10.593(2) Å, b= 14.377(3) Å, c= 17.872(4) Å, α= 104.41(2)°, β= 90.55(2)°, γ= 106.91(2)°, V= 2512.4 ų, Z=4. X-Ray crystallographic studies shows the presence of four molecules in the asymmetric unit consisting of two pairs of diastereomeric peptides, Boc-l -Ala-l -Ile-Aib-OMe and Boc-l -Ala-d -Ile-Aib-OMe. The four molecules in the asymmetric unit form a rarely found mixed antiparallel and parallel β-sheet hydrogen bond motif. The Ala and (l ,d )-Ile residues in all the four molecules adopt the extended conformations, while the φ, ψ values of the Aib residues are in the right-handed helical region. In one of the molecules the Ile sidechain adopts the unusual gauche conformation about the C^β-C^γ bond. © Munksgaard 1996.     

The crystal structure of Boc-Pro-Val-Gly-NH2, with a remark on the conformation of the valyl residues in peptides

The crystal structure of Boc-Pro-Val-Gly-NH₂ has been determined: monoclinic; P2₁; a = 9.331 (3) Å, b = 9.532 (4), c = 23.080 (9), β= 91.33 (3)R, Z = 4; R = 0.053 for 3400 reflections with ˙Fo˙,>α(Fo). There are two independent but very similar molecules in the crystal. The peptide main chains are in an extended form, and packed in two kinds of antiparallel β sheets, the (φ, Φ) angles of the central Val residues are (-156°, 146°) and (-139°, 155°), and the mean length of the N- H . 0 hydrogen bonds in the sheets is 2.965 Å. A detailed study of the conformations of the Val residues in oligopeptide crystals shows that the preferred conformation of Val in peptides is: the (φ, Φ) angles close to those of the antiparallel β sheet, and C^γ1 and C^γ2, against N with respect to the C^α– C^β bond, at either (trans, gauche) or (-gauche, gauche). The mean π(NC^αC') angle of such Val residues is 107.9(9)°. A twisting in the β sheets is also discussed.     

Structure and conformation of linear peptides

The tripeptide, glycyl-glycyl-L-isoleucine, crystallizes as a monohydrate in the monoclinic space group P2₁, with a = 12.746(2), b = 6.172(1), c = 8.643(1) Å, β = 99.77(2)°, and Z = 2. The structure was solved by direct methods and refined to an R-value of 0.039 for 917 (I > 1°) reflections. The molecule exists as a zwitterion in the crystal. The peptide units are trans and show significant deviations from planarity. The plane of peptide units and of the carboxyl group are nearly mutually perpendicular to each other. The peptide backbone torsion angles are: ø₁ = - 171.2°, ω₁ = - 176.8°, ø₂ = - 106.1°, ø₂ = - 150.7°, ø₂ = - 172.1°, ø₃ = - 70.9°, ø₃ = 136.5°. For the side-chain of isoleucine, ø₁ = - 58.1°, ø₂ = 169.7° and the system of bonds C′-C^α-C^β-C γ₁^-Cδ is trans zig-zag. The packing arrangement involves spatial segregation of polar and nonpolar moieties.     

Crystal structure of tert.-butyloxycarbonyl-L-prolyl-D-alanyl-D-alanyl-N-methylamide Dimeric β-sheet formation

The crystal structure of the tripeptide t-Boc-L-Pro-D-Ala-D-Ala-NHCH₃, monohydrate, (C₁₇H₃₀N₄O₅·H₂O, molecular weight = 404.44) has been determined by single crystal X-ray diffraction. The crystals are mono-clinic, space group P2₁, a = 9.2585(4), b = 9.3541(5). c = 12.4529(4) Å, β= 96.449(3)°, Z = 2. The peptide units are in the trans and the tBoc-Pro bond in the cis orientation. The first and third peptide units show significant deviations from planarity (Δω=5.2° and Δω=3.7°, respectively). The backbone torsion angles are: φ¹, = -60°, ψ_1/= 143.3°, ω₁= -174.8°, φ₂= 148.4°, ψ₂= -143.1°, ω₂= -179.7°, φ₃= 151.4°, ψ₃= -151.9°, ω₃= -176.3°. The pyrrolidine ring of the proline residue adopts the C₂— C^γ conformation. The molecular packing gives rise to an antiparallel β-sheet structure formed of dimeric repeating units of the peptide. The surface of the dimeric β-sheet is hydrophobic. Water molecules are found systematically at the edges of the sheets interacting with the urethane oxygen and terminal amino groups. Surface catalysis of an L-Ala to D-Ala epimerization process by water molecules adsorbed on to an incipient β-sheet is suggested as a mechanism whereby crystals of the title peptide were obtained from a solution of tBoc-Pro-D-Ala-Ala-NHCH₃.     

Synthesis and crystal structures of Boc-L-Asn-L-Pro-OBzl·CH3OH and dehydration side product,Boc-β-cyano-L-alanine-L-Pro-OBzl

Boc-L-Asn-L-Pro-OBzl:C₂₁H₂₉O₆N₃·CH³OH, M_r= 419.48 + CH₃OH, monoclinic, P2₁, a= 10.049(1), b= 10.399(2), c= 11.702(1)Åβ= 92.50(1)°, V = 1221.7(3)ų, d_x= 1.14g cm^-3, Z = 2, CuKα (λ= 1.54178 Å), F(000) = 484 (with solvent), 23°, unique reflections (I > 3σ(I)) = 1745, R = 0.043, R_w= 0.062, S = 1.66. Boc-β-cyano-L-alanine-L-Pro-OBzl: C₂₁H₂₇O₅N₃, M_r= 401.46, orthorhombic, P2₁2₁2₁, a= 15.741(3), b= 21.060(3), c= 6.496(3)ÅV= 2153(1)ų, d_x= 1.24g·cm^-3, Z = 4, CuKα (λ= 1.54178 Å), F(000) = 856, 23°, unique reflections (I > 3σ(I)) = 1573, R = 0.055, R_w= 0.078, S = 1.86. The tert.-butyloxycarbonyl (Boc) protected dipeptide benzyl ester (OBzl), BOC-L-Asn-L-Pro-OBzl, prepared from a mixed anhydride reaction using isobutylchloroformate, BOC-L-asparagine, and HCI·L-proline-OBzl, crystallized with one methanol per asymmetric unit in an extended conformation with the Asn-Pro peptide bond trans. Intermolecular hydrogen bonding occurs between the methanol and the Asn side chain and between the peptide backbone and the Asn side chain. A minor impurity due to the dehydration of the Asn side chain to a β-CNaia crystallized with a similar extended conformation and a single intermolecular hydrogen bond.     

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.     

Conformational investigation of α, β-dehydropeptides

The crystal structure of Ac-Pro-ΔVal-NHCH₃ was examined to determine the influence of the α,β-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4° in needle-shaped form in orthorhombic space group P2₁2₁2₁ with a= 11.384(2) Å, b = 13.277(2) Å, c = 9.942(1) Å. V = 1502.7(4) ų Z = 4, D_m= 1.17 g cm^?3 and D_c=1.18 g cm^?3 The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a β-bend between the type I and the type III conformation with φ₁=?68.3(4)°, ψ₁=? 20.1(4)°, φ₂=?73.5(4)°= and Ψ₂=?14.1(4)°=. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i+ 3)th residue stabilizes the β-bend. An additional intermolecular N.,.O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single α,β-dehydroamino acid residue in the (i+ 2) position and forming a β-bend reveal a type II conformation.     

Conformation and hydrogen bonding of N-formylpeptides: crystal and molecular structure of N-formyl-l-alanyl-l-aspartic acid†

Crystals of N-formyl-l -alanyl-l -aspartic acid (C₈H₁₁N₂O₆) grown from aqueous methanol solution are orthorhombic, space group, P2₁2₁2₁ with cell parameters at 294 K of a = 13.619(2), b = 8.567(2), c = 9.583(3)Å, V = 1118.1ų, M.W. = 232.2, Z = 4, D_m= 1.38g/cm³ and D_x= 1.378g/cm³. The crystal structure was solved by the application of direct methods and refined to an R value of 0.075 for 1244 reflections with I ≥ 3σ collected on a CAD-4 diffractometer. The structure contains two short inter-molecular hydrogen bonds: (i) between the C-terminal carboxyl OH and the N-acyl oxygen (2.624(3)Å), a characteristic feature found in many N-acyl peptides and (ii) between the aspartic carboxyl OH and the peptide oxygen OP1 (2.623(3)Å). The peptide is nonplanar (ω= 165.5(6)°). The molecule takes up a folded conformation in contrast to N-formyl peptides which form extended β-sheets; the values of ø₁, Ψ₁, ø₂, Ψ¹₂, and Ψ²₂ are, respectively –65.7(6), 152.0(5), –107.2(5), 30.9(5), and –150.3(6). The aspartic acid side chain conformation is g^? with χ¹= 73.1(5). The formyl group, as expected, is transplanar [OF-CF-N1-CA1 = -4.0(8)°]. The presence of the short O–H … O hydrogen bond emerges as a structural feature common to this peptide and several other N-formyl peptides. There are no C-H … O hydrogen bonds in this structure.     

Parallel and antiparallel aggregation of α-helices

An apolar helical decapeptide with different end groups, Boc- or Ac-, crystallizes in a completely parallel fashion for the Boc-analog and in an antiparallel fashion for the Ac-analog. In both crystals, the packing motif consists of rows of parallel molecules. In the Boc-crystals, adjacent rows assemble with the helix axes pointed in the same direction. In the Ac-crystals, adjacent rows assemble with the helix axes pointed in opposite directions. The conformations of the molecules in both crystals are quite similar, predominantly α-helical, except for the tryptophanyl side chain where χ¹? 60° in the Boc- analog and ? 180° in the Ac-analog. As a result, there is one lateral hydrogen bond between helices, N(lε)…O(7), in the Ac-analog. The structures do not provide a ready rationalization of packing preference in terms of side-chain interactions and do not support a major role for helix dipole interactions in determining helix orientation in crystals. The crystal parameters are as follow. Boc-analog: C₃H₇,N₁₁O₁₃ C₃H₇OH, space group P1 with a = 10.250(3) Å, b = 12.451(4) Å, c = 15.077(6) Å, x= 96.55(3)°, β= 92.31(3)°, y= 106.37(3)°, Z = 1, R = 5.5% for 5581 data (|F| > 3.0a(F)), resolution 0.89 Å. Ac-analog: C₅₇,H₉₁,N₁₁,O₁₂, space group P2₁, with a = 9.965(1) Å, b = 19.707(3) Å, c = 16.648(3) Å, β= 94.08(1), Z = 2, R = 7.2% for 2530 data (|F| > 3.0σ(F)), resolution 1.00 Å.     

Structure and conformation of linear peptides VII.

The tripeptide, L-valyl-glycyl-glycine (C₉H₁₇N₃O₄, molecular weight = 231), crystallizes in the monoclinic space group C2, with a = 24.058(3)Å, b = 4.801(1), c = 10.623(2), β = 110.02(1)° and Z = 4. The structure was determined by direct methods and refined to a final R-index of 0.043 for 830 reflections (sinθ/Λ ≤ 0.53 A^-1) with I> 1.0s?. The molecule exists as a zwitterion. The peptide units are trans and one of them shows significant deviations from planarity (Δω₂ = 9.3°). The peptide chain repeat distance, 1C^α-3Cα, is 7.23Å and the molecule displays a highly extended conformation with backbone torsion angles of ψ₁ = 123.1°, ω₁ = - 179.4°, ø₂ = - 155.1°, ψ;₂ = 154.7°, ω₂ = 170.7°, ø₃ = - 146.6° and ψ₃ = 180.0°. For the valyl side chain, χ₁₁ = - 52.5°, χ₁₂ = 174.2°. The packing involves hydrogen-bonded interactions between successive molecules related by the β-translation of the lattice, giving rise to the familiar parallel β-sheet structure which appears to be the most extended one observed to date.     

Structure of N-Boc-L-Pro-dehydro-Leu-NHCH3

The peptide N-Boc-L-Pro-dehydro-Leu-NHCH₃ was synthesized to examine the nature of β-bend as a result of dehydro-Leu in the sequence. The peptide crystallizes from methanol-water mixture at 4° in orthorhombic space group P22₁2₁ with a = 5.726(1)Å, b = 14.989(4) Å, c = 24.131(9) Å, V = 2071(1) ų, Z = 4, dm = 1.064(5)gcm^-3 and dc = 1.0886(5)gcm^-3. The structure was solved by direct methods using SHELXS 86 and it was refined by full-matrix least-squares procedure to an R value of 0.059 for 957 observed reflections. The peptide is found to adopt a β-bend type II conformation with φ₁=– 51(1)°, ψ₁= 133(1)°, φ₂= 74(2)° and ψ₂= 8(2)°. The β-bend is stabilized by an intra-chain hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue. The five-membered pyrrolidine ring of Pro-residue adopts an ideal C^γ-exo conformation with torsion angles of χ₁¹=– 25(1)°, χ₁²= 38(1)°, χ₂=– 34(1)°, χ₁⁴= 20(1)° and χ₁⁰= 2(1)°. The side chain conformation angles of dehydro-Leu residue are χ₂= 12(2)°, χ₂^2.1=– 112(2)° and χ₂^2.2= 136(2)°. The crystal structure is stabilized by a network of hydrogen bonds and van der Waals interactions.     

Structure and conformation of linear peptides. X. Structure of glycyl-glycyl-L-phenylalanine hydrochloride

The crystal structure of a tripeptide, glycyl-glycyl-L-phenylalanine HCl (C₁₃H₁₈N₃O₄ ± HCl, molecular weight = 316.5) has been determined. The crystals are orthorhombic, space group P2₁2₁2₁, with a = 4.877 (2) Å, b = 9.956(3), c = 32.690(5) and Z = 4. The final R-index is 0.043 for 1325 reflections (sinØ/Λ ± 0.55 Å^-1) with I > 2.0 s? (I). The N-terminal of the molecule is protonated and the C-terminal exists in an un-ionised state. The peptide units are trans and one of them shows significant deviations from planarity (¶Δω₁¶ = 11.3°). The peptide backbone is folded with torsion angles of: ø₁ = 165.5°, ω₁ = — 168.7°, ø₂ = 63.6°, ø₂ = — 153.6°, ω₂ = 176.5°, ø₃ = — 72.2° and Φ₃ = 166.5°. For the side chain of phenylalanine, X₁ = — 79.5° and X₂ = 86.8°. An intramolecular water bridge links the two ends of the molecule.     

Structure of cyclic peptides: the crystal and solution conformation of cyclo(Phe-Phe-Aib-Leu-Pro)

A solid-state and solution conformation analyses of the cyclopentapeptide cyclo(Phe-Phe-Aib-Leu-Pro) has been carried out by X-ray diffraction and nuclear magnetic resonance techniques. The structure of the hexagonal crystals, grown from a methanol solution [a=b= 16.530(4) Å, c= 21.356(9) Å, space group P6₅, Z = 6], shows the presence of one intramolecular N-H?O=C hydrogen bond with the formation of a γ-turn (C₇). The Aib³ residue, at the center of the γ-turn, presents unexpected values of the torsion angles [φ= 70.5° and ψ= -73.8°], which have been observed only once before for this helicogenic residue. A cis peptide bond occurs between Leu⁴ and Pro⁵; all other peptide bonds are trans. The overall conformation for the cyclopentapeptide with one cis-peptide bond on one side and an intramolecular γ-turn on the opposite side results in an equatorial topology of the side-chains of the Phe¹, Phe² and Leu⁴ residues. Indeed, the C^α-C^βand C^β-C^γ bonds of these residues lie approximately in the mean plane of the cyclic ring system. The structure is compared with data in the literature on cyclic pentapeptides. In addition the Pro-Phe-Phe moiety shows a conformation similar to that observed in other larger cyclic bioactive peptides, which indicates a reduced number of conformations for this sequence. The solution study was carried out in three different solvent systems: chloroform, acetonitrile and methanol in the temperature interval 220–300 K. In all three solvents the room temperature spectra show that the peptide is conformationally nonhomogeneous. In acetonitrile at low temperatures it is possible to reduce the conformational equilibrium to two predominant conformers which differ for the cis-trans isomerism of the Leu⁴-Pro⁵ peptide bond.     

Channel‐forming,self‐assembling,bishelical amphiphilic peptides: design,synthesis and crystal structure of Py(Aibn)2, n = 2, 3, 4

Abstract: The design, synthesis, characterization and self‐assembling properties of a new class of amphiphilic peptides, constructed from a bifunctional polar core attached to totally hydrophobic arms, are presented. The first series of this class, represented by the general structure Py(Aib_n)₂ (Py = 2,6‐pyridine dicarbonyl unit; Aib = α, α′‐dimethyl glycine; n = 1–4), is prepared in a single step by the condensation of commercially available 2,6‐pyridine dicarbonyl dichloride with the methyl ester of homo oligoAib peptide (Aib_n‐OMe) in the presence of triethyl amine. ¹H NMR VT and ROESY studies indicated the presence of a common structural feature of 2‐fold symmetry and an NH…N hydrogen bond for all the members. Whereas the Aib3 segment in Py(Aib3)₂ showed only the onset of a 3₁₀‐helical structure, the presence of a well‐formed 3₁₀‐helix in both Aib4 arms of Py(Aib4)₂ was evident in the ¹H NMR of the bispeptide. X‐ray crystallographic studies have shown that in the solid state, whereas Py(Aib2)₂ molecules organize into a sheet‐like structure and Py(Aib3)₂ molecules form a double‐stranded string assembly, the tetra Aib bispeptide, Py(Aib4)₂, is organized to form a tetrameric assembly which in turn extends into a continuous channel‐like structure. The channel is totally hydrophobic in the interior and can selectively encapsulate lipophilic ester (CH₃COOR, R = C₂H₅, C₅H₁₁) molecules, as shown by the crystal structures of the encapsulating channel. The crystal structure parameters are: 1b , Py(Aib2)₂, C₂₅H₃₇N₅O₈, sp. gr. P2₁2₁2₁, a = 9.170(1) Å, b = 16.215(2) Å, c = 20.091(3) Å, R = 4.80; 1c , Py(Aib3)₂, C₃₃H₅₁N₇O₁₀·H₂O, sp. gr. P, a = 11.040(1) Å, b = 12.367(1) Å, c = 16.959(1) Å, α = 102.41°, β = 97.29°, γ = 110.83°, R₁ = 6.94; 1 da, Py(Aib4)₂?et ac, C₄₁H₆₅N₉O₁₂?1.5H₂O·C₄H₈O₂, sp. gr. P, a = 16.064(4) Å, b = 16.156 Å, c = 21.655(5) Å, α = 90.14(1)°, β = 101.38(2)°, γ = 97.07(1)°, Z = 4, R₁ = 9.03; 1db, Py(Aib4)₂?amylac,C₄₁H₆₅N₉O₁₂?H₂O ·C₇H₁₄O₂, P2₁/c, a = 16.890(1) Å, b = 17.523(1) Å, c = 20.411(1) Å, β = 98.18 °, Z = 4, R = 11.1 (with disorder).     

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 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.     

Ten-membered cyclotripeptides

The 10-membered cyclotripeptide cyclo(-βAla-Phe-Pro-) (III) has been synthesized by cyclizing under mild conditions the linear precursor βAla-Phe-Pro-Onp·TFA. Crystal and molecular structure of (III) is reported and compared with that of the related models cyclo-(-MeAnt-Phe-Pro-) (I) and cyclo(-Hyb-Phe-Pro-) (II). Crystals of (III) are orthorhombic, C222₁, with a= 8.224(1), b= 14.056(2), c= 28.559(3)A and Z = 8. The backbone of (III) is characterized by a cis-cis-trans conformation. Both the βAla-Phe and Phe-Pro peptide bonds are cis with ω values of – 14.4° and –0.1°, whereas the Pro-βAla junction exhibits trans conformation with high deviation from planarity (ω= 158.6°). The pyrrolidine ring has C₂-C^β-endo-C^γ-exo conformation and the benzylic side chain is extended toward the Phe-CO group. The molecular conformation of (III) shows a striking resemblance to that of the heterodetic model (II) and strongly differs from the all-cis conformation shown by the homodetic analogue (I).     

Monoclinic polymorph of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe(anhydrous)

The structures of two crystal forms of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe have been determined. The triclinic form (PI, Z= l) from DMSO/H₂O crystallizes as a dihydrate (Karle, Sukumar & Balaram (1986) Proc. Natl. Acad. Sci. USA 83, 9284-9288). The monoclinic form (P2¹, Z = 2) crystallized from dioxane is anhydrous. The conformation of the peptide is essentially the same in both crystal systems, but small changes in conformational angles are associated with a shift of the helix from a predominantly α-type to a predominantly 3₁₀-type. The r.m.s. deviation of 33 atoms in the backbone and Cβ positions of residues 2-8 is only 0.29 Å between molecules in the two polymorphs. In both space groups, the helical molecules pack in a parallel fashion, rather than antiparallel. The only intermolecular hydrogen bonding is head-to-tail between helices. There are no lateral hydrogen bonds. In the P2₁ cell, a = 9.422(2)Å, b = 36.392(11)Å, c = 10.548(2)Å, β= 111.31(2)° and V = 3369.3ų For 2 molecules of C⁶⁰H⁹⁷N¹¹O¹⁰ per cell.     

Peptide crystal growth via vapor diffusion

The structure of a dihydrated form of glycyl-L-tyrosyl-L-alanine (GYA) has been determined as part of a series of peptide structural investigations and development of microscale vapor diffusion experiments for peptide crystal growth. Crystals were grown by the hanging-drop method against sodium acetate. The tripeptide is a zwitterion in the crystal, adopting an extended conformation through glycine, a nearly perpendicular bend attyrosine and a reverse turn for the C-terminal carboxylate. Principal backbone torsion angles are ψ₁ 175(1)°, ω₂ 173(1)°, φ₂ -119(1)°, ψ₂ 120(1)°, ω₃3 172(1)°, φ₃ -73(1)°,ψ₃₁ -9(1)°, ψ₃₂ 171(1)°. The tyrosyl side chain adopts an unusual orientation (χ^1/2= -86(1)°). The relationship of the GYA.2H₂O structure to GYA sequences in proteins is examined, particularly as regards its helix-forming potential. Crystal data: C₁₄H₁₉N₃O₄.2H₂O, Mr = 345.36, orthorhombic, P2₁2₁2₁, a = 4.810 (4), b= 11.400(7), c = 30.162(23)Å, V=1653.8(24)Å^?3, Z = 4, Dx= 1.387 Mgm^?3, λ(CuK_α^?)= 1.540 Åμ= 9.053 mm^?1, F(000) = 736, T = 199K, R = 0.041 for 1458 observations with I ≥ 3σ(I).     

Conformation and crystal structure of L-prolyl-L-glutamic acid dihydrate

The crystal structure of the dipeptide L-prolyl-L-glutamic acid dihydrate, L-Pro-L-Glu · 2H₂O, C₁₀H₂₀O₇N₂, has been determined from three-dimensional X-ray diffractometer data. The dipeptide crystallizes in the space group P2₁ of the monoclinic system with two formula units in a cell of dimensions a= 5.629(2), b= 11.832(5), c= 10.485(4)Å, and β= 103.06(3)°. The structure was solved by direct methods and refined by least squares techniques to a final value of the conventional R-factor (on F) of 0.039 based on 1798 independent intensities with I ≥ 3s?(I). The dipeptide occurs as a zwitterion in the crystal with the pyrrolidine nitrogen atom protonated and the main chain carboxyl group deprotonated. The conformation of the peptide linkage is trans, the ω torsional angle being 173.7°. The pyrrolidine ring adopts the C_s-C^β endo conformation and the conformation of the glutamyl side chain is fully extended. There is considerable intermolecular hydrogen bonding in the crystals.