Structure and conformation of peptides involving prolyl residue

The dipeptide, L-prolyl-L-leucine monohydrate (C₁₁ H₂₀ N₂ O₃· H₂O, molecular weight, 246.3) crystallizes in the monoclinic space group P2_1/, with cell constants: a = 6.492(2)Å b = 5.417(8)Å c = 20.491(5)Å, β= 96.59(2)°, Z = 2, Do = 1.15g/cm³, and Dc = 1.142g/cm³. The structure was solved by SHELX-86 and refined by full matrix least squares methods to a final R-factor of 0.081 for 660 unique reflections (I > 2σ (I)) measured on an Enraf Nonius CAD-4 diffractometer (CuK_x, λ= 1.5418 4AR, T = 293 K). The peptide linkage exists in the trans conformation. The pyrrolidine ring exists in the envelope conformation. The values of the sidechain torsion angles are: ψ₁= -59.3(13)°, ψ₂₁= -63.1(16)° and ψ₂₂= 174.8(15)° for leucine (C-terminal). The crystal structure is stabilised by a three-dimensional network of N—H… O, O—H… O, and C—H…O hydrogen bonds.     

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.     

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

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

Cystine peptides Antiparallel β-sheet conformation of the cyclic biscystine pep tide [Boc-Cys-Ala-Cys-NHCH3]2

The crystal structure analysis of the cyclic biscystine peptide [Boc-Cys¹-Ala²-Cys³-NHCH₃]₂ with two disulfide bridges confirms the antiparallel β-sheet conformation for the molecule as proposed for the conformation in solution. The molecule has exact twofold rotation symmetry. The 22-membered ring contains two transannular NH ? OC hydrogen bonds and two additional NH ? OC bonds are formed at both ends of the molecule between the terminal (CH₃)₃COCO and NHCH₃ groups. The antiparallel peptide strands are distorted from a regularly pleated sheet, caused mainly by the L-Ala residue in which φ=– 155° and ψ= 162°. In the disulfide bridge C^α (1)-C^β (1)-S(1)-(3′)-C^β(3′)-C^α(3′), S—S = 2.030 Å, angles C^β SS = 107° and 105°, and the torsional angles are –49, –104, +99, –81, –61°, respectively. The biscystine peptide crystallizes in space group C2 with a = 14.555(2) Å, b = 10.854(2) Å, c = 16.512(2)Å, and β= 101.34(1) with one-half formula unit of C₃₀H₅₂N₈O₁₀S₄· 2(CH₃)₂SO per asymmetric unit. Least-squares refinement of 1375 reflections observed with |F| > 3σ(F) yielded an R factor of 7.2%.     

Backbone—side-chain interactions in serine Synthesis,crystal structure and solution conformation of a linear model peptide N-Boc-l-Ser-l-Phe-OCH3

The peptide Boc-Ser-Phe-OCH₃ was synthesised by a solution-phase method using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, space group P2₁ with a= 5.128(2), b=17.873(2), c=11.386(2) Å, and β=98.03(3)°. The structure was determined by direct methods and refined by a structure factor least-squares procedure. The final R-value for 1499 observed reflections was 0.041. The structure contains one peptide and one solvent water molecule. The peptide adopts a β-strand-like conformation with φ₁=- 100.3(5), ψ_l= 99.9(5), φ₂= - 122.2(5), ψ^T₂= -172.5(6)°. The Ser side-chain assumes an extended conformation with χ¹₁= - 177.0(4)°. The O^γH group of serine acts as a proton donor in an intramolecular weak hydrogen bond with (Ser) O′₁; [O^γ₁;-H^γ₁?O′₁= 3.253(6) Å]. The Phe side-chain adopts a staggered conformation with χ¹₂= -70.9(6), χ²_2,1= 88.4(7)°, χ^2,2₂= -89.2(6)°. The water molecule generates a loop through two hydrogen bonds with O^γ₁ [OW?O^γ₁= 2.893(5) Å] and O′₂ [OW-O′₂= 2.962(7) Å] atoms. The unit-translated peptide molecules along the α-axis are held by hydrogen bonds: N₁-H₁?O₂ (x-1, y, z) = 2.954(4) Å and N₂-H₂?O′₁ (x+1, y, z) = 2.897(6) Å in a manner similar to those observed in parallel β-pleated sheet structures. There is an additional interaction involving O^γ₁ and the water molecule [OW?O^γ₁ (x= 1, y, z) = 2.789(4) Å]. The strong NOE peak of C_i(H)?N_i+1 (H) and a simultaneous weak NOE peak of N_i(H)?N_i+l (H) in the ROESY spectra of two-dimensional NMR in dimethyl sulfoxide indicate a β-strand-like conformation for the peptide in solution. © Munksgaard 1996.     

Structure and conformation of linear peptides. IX. Structure of l-tyrosyl-l-phenylalanine

The dipeptide, l -tyrosyl-l -phenylalanine (C₁₈H₂₀N₂O₄, molecular weight = 346) crystallizes as a monohydrate in the orthorhombic system, space group P2₁2₁2₁ with a = 5.744(2), b = 8.284(2), c = 35.518(6)Å, Z = 4. The structure was solved by direct methods and refined to a final R-index of 0.060. The peptide unit is trans and planar, and makes a dihedral angle of 93° with the plane of the carboxyl group. The backbone torsion angles are given by: ø₁ = 164.7°, ω₁ = 177.0°, φ₂ = – 70.1°, ø₂ = 146.6°. The values of the side-chain torsion angles (χ₁, χ₂) are (47.3°, 79.9°) for tyrosine and (– 75.1°, 75.9°) for phenylalanine. The planes of the two (side-chain) aromatic rings make a dihedral angle of 142.6° and their centres are separated by 9.3 Å.     

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.     

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.     

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 and conformation of linear peptides

The crystal structure of t-Boc-glycyl-L-phenylalanine (C₁₄H₂₂N₂O₅, molecular weight = 298) has been determined. Crystals are monoclinic, space group P2₁, with a = 7.599(1)Å, b = 9.576(2), c = 12.841(2), β = 97.21(1)°, Z = 2, D_m = 1.149, D° = 1.168 g · cm^-3. Trial structure was obtained by direct methods and refined to a final R-index of 0.064 for 1465 reflections with I> 1s?. The peptide unit is trans planar and is nearly perpendicular to the plane containing the urethane moiety. The plane of the carboxyl group makes a dihedral angle of 16.0° with the peptide unit. The backbone torison angles are ω₀ = - 176.9°, ø₁ = - 88.0°, ψ₁ = - 14.5°, ω1 = 176.4°, ø₂ = - 164.7° and ψ2 = 170.3°. The phenylalanine side chain conformation is represented by the torsion angles χ₁ = 52.0°, χ₂ = 85.8°.     

New patterns of hydrogen bonded interactions between polypeptide chains

Crystals of glycylglycylglycine (C₆H₁₁N₃O₄), grown from an aqueous methanol solution, are triclinic, space group P1, with the unit cell dimensions (at 22 ± 3°) a= 11.656(3), b= 14.817(3), c= 4.823(2) Å, α= 88.45(3), β= 95.96(3), γ= 105.42(3)°, Z = 4 (with two molecules in the asymmetric unit) with a density of D_obs= 1.58g·cm^-3 and D_calc= 1.572g·cm^-3. The crystal structure was solved by a combination of multisolution and trial and error methods and refined with full-matrix least-squares method to a final R value of 0.036 for the observed 3021 reflections (I ≥ 2s?). The conformation of the two molecules I and II in the asymmetric unit is very similar (except around the N-terminal end); they have the fully extended trans-planar conformation, and have ω values ranging from 2 to 4°. The peptide chain repeating distances (C¹_α - C³_α) are 7.27 Å and 7.18 Å in the two molecules as compared with the value of 6.68 Å for extended β-sheets with β-carbons. There are four different interactions between these two molecules characterized by different hydrogen bonding. Molecule I is hydrogen bonded to a neighboring molecule I using four hydrogen bonds. Molecule II is hydrogen bonded to another II, using bifurcated interactions involving the peptide nitrogen. Molecule I is hydrogen bonded to two different molecules II forming distinctly different hydrogen bonding patterns from the two mentioned above. The molecules are packed in rows, in a head-to-tail fashion (C-terminal opposite N-terminal) and are held together in sheets by hydrogen bonds between carbonyl and amide groups, corresponding to the very familiar anti-parallel pleated sheet arrangement for polypeptides. The hydrogen bonds involving the amino nitrogens as donors are significantly longer and presumably weaker compared to those involving the NH⁺₃ group. The C=O distances show variations that correlated with hydrogen bonding. The N-H … O angle varies from 152 to 174° and the bent N-H … O hydrogen bonds show bifurcated interactions.     

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.     

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.     

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.     

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.     

Structure and conformation of linear peptides XII. Structure of tryptophanyl-glycyl-glycine dihydrate

The crystal structure of a tripeptide, tryptophanyl-glycyl-glycine dihydrate (C₁₅H₁₈N₄O₄·2H₂O, molecular weight = 354) has been determined. The crystals are orthorhombic, space group P2₁2₁2₁ with a= 7.875 (1) A,b= 9.009(1), c= 24.307(1) and Z = 4. The final R-index is 0.058 for 1488 reflections ((sin θ/λ≤ 0.6 A^?1) with I < 2σ(I). The molecule exists as a zwitterion, with terminal NH⁺₃ and COO^? groups. The peptide units are trans and nearly perpendicular to the plane of the carboxyl group. The backbone torsion angles are: ψ₁= 132.7°, ω₁= 174.2°, φ₂ 88.2°, ψ= 8.6°, ω₂ - 179.8°, φ= - 85.2°, ψ₃₁, = - 178.1°, ψ₃₂ 5.0°. For the sidechain of tryptophan, χ₁= - 171.6°, χ₂ 101.0°.     

Conserved and novel structural characteristics of enantiomorphic Leu-enkephalin

The crystal of the Leu-enkephalin raceinate (L-Tyr-Gly-Gly-L-Phe-L-Leu and d -Tyr-Gly-Gly-D-Phe-D-Leu) was obtained as a centrosymmetric space group. Crystal data: C₂₈H₃₇N₅O₇· 1.5H₂O, M_w, = 582.6, triclinic, space group PI, a = 11.176(3), b = 16.115(3), c = 10.204(4) Å, α= 92.41(3), β= 104.86(2), γ= 85.35(2) °, V= 1770(1) ų, Z= 2; F(000) = 640, μ(CuKα) = 6.50 cm^?1, D_x= 1.081 g cm^?3. The structure was determined by X-ray diffraction. The conformation of the Leu-enkephalin racemate was classified into the extended form which has been often observed in natural enkephalin. The symmetry-related molecules were connected by hydrogen bonds and arranged in an antiparallel fashion. The molecular packing showed a sheet structure similar to that of natural enkephalin.     

Intramolecular water bridge and a distorted trans peptide bond in the crystal structure of α-L-glutamyl-L-aspartic acid hydrate

The crystal structure of the monohydrated form of α-L-glutamyl-L-aspartic acid, C₁₉H₁₄N₂O₇ · H₂O, has been determined from three-dimensional X-ray diffractometer data. The dipeptide crystallizes in the triclinic space group P1 with one formula unit in a cell of dimensions a = 7.806(3), b = 8.473(5), c = 4.965(2)Å, α = 101.50(3), β = 100.81(3), γ = 104.72(3)°. The structure was solved by direct methods and refined by full-matrix least-squares methods to a final value of the weighted R factor (on F) of 0.047 based on 1647 unique observations with I ≥ 0.01 (I). The dipeptide crystallizes as a zwitterion with the amino terminus protonated and the main chain carboxyl group ionized. The peptide bond conformation is trans, though the ω angle of 161.3° is highly distorted from the ideal 180° value. The adoption of an unusual 13-membered “intramolecularly” hydrogen bonded ring structure with resulting α-turn character is responsible for distortion of the peptide bond. The solid-state conformation of the hydrate thus differs considerably from the previously reported unhydrated pseudopolymorphic structure of α-L-Glu-L-Asp.     

Structure and conformation of linear peptides

The crystal structure of a dipeptide tert-butyloxycarbonyl-l -alanylglycine monohydrate (C₁₀H₁₈N₂O₅·H₂O), molecular weight 264, has been determined. The crystals are monoclinic, space group P2₁, with a= 10.767(1), b= 6.317(1), c= 10.981(2) Å, β= 109.15(2)°, and Z= 2, D_c= 1.24 g cm^?3. The structure was solved by direct methods and refined to 3 final R-index of 0.045 for 856 reflections (sin θ/λ < 0.55 Å^?1) with I > 2 σ. The N-terminus of the molecule blocked with the t-Boc group is uncharged and the C-terminus exists in an unionized state. The peptide unit is trans and shows slight deviations from planarity. (Δω= 3.1°). The peptide backbone is folded, with torsion angles of φ₁= -76.0(5), ψ₁= 164.3(4), ω₁= 176.9(5), φ₂= 116.1(5), ψ₂₁= - 2.8(7) and ψ₂₂= 177.8(4)°. The conformation about the urethane bond (C5–N1) is trans. The urethane group is essentially planar. The conformation of the boc group is trans–trans.     

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).