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.     

Conformational investigation of α,β-dehydropeptides VII*. Conformation of Ac-Pro-ΔAla-NHCH3 and Ac-Pro-(E)-ΔAbu-NHCH3: comparison with (Z)-substituted α,β-dehydropeptides†

The crystal structure and solution conformation of Ac-Pro-ΔAla-NHCH₃ and the solution conformation of Ac-Pro-(E)-ΔAbu-NHCH₃ were investigated by X-ray diffraction method and NMR, FTIR and CD spectroscopies. Ac-Pro-ΔAla-NHCH, adopts an extended-coil conformation in the crystalline state, with all-trans peptide bonds and the ΔAla residue being in a C₅ form, φ₁=– 71.4(4), ψ₁=– 16.8(4), φ₂=– 178.4(3) and ψ₂= 172.4(3)°. In inert solvents the peptide also assumes the C₅ conformation, but a γ-turn on the Pro residue cannot be ruled out. In these solvents Ac-Pro-(E)- ΔAbu-NHCH₃ accommodates a βII-turn, but a minor conformer with a nearly planar disposition of the CO—NH and C=C bonds (φ₂～0°) is also present. Previous spectroscopic studies of the (Z)-substituted dehydropeptides Ac-Pro-(Z)- ΔAbu-NHCH, and Ac-Pro-ΔVal-NHCH₃ reveal that both peptides prefer a βII-turn in solution. Comparison of conformations in the family of four Ac-Pro-ΔXaa-NHCH₃ peptides let us formulate the following order of their tendency to adopt a β-turn in solution: (Z)- ΔAbu > (E)- δAbu > ΔVal; ΔAla does not. None of the folded structures formed by the four compounds is stable in strongly solvating media. © Munksgaard 1996.     

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.     

The linked φψ chain plot for visual comparison of the backbone conformation of peptides and proteins

A new graphic method is described for presenting in two dimensions the φ and ψ dihedral angles that describe the backbone conformation of a peptide or protein chain. For each residue in sequence, φ and ψ are plotted as dots on the y-axis above the next two points on the x-axis representing the residue number. Each dot is linked to the next dot by a slanting line segment (link) and each cis-peptide bond (ω～0°) between residues X and Y is indicated by marking dots ψx and φy with a diamond. This linked φ and ψ chain plot is more useful than an unlinked φ and ψ chain plot for visually recognizing helices, sheets and turns and for graphically comparing several protein structures. Overlaying the linked φ and ψ chain plots for 15 β-hairpins classified as type-I' β-turns revealed that three were significantly different from the rest. The dihedral angles (mean f standard deviation) of the loop residues (L1, L2) for a cluster of 12 β-hairpins with an inverse-common, type-I′β-turn (φ_L1= 52±7°, ψ_L1=40±8°, φ_L2=80±9°, ψ_L2= -1±13°) are similar to the standard dihedral angles for the type-1′ turn (60, 30, 90 and 0°, respectively).     

Conformations of peptides containing 1-aminocyclohexanecarboxylic acid (Acc6). Crystal structures of two model peptides

The crystal structures of two peptides containing 1-aminocyclohexanecarboxylic acid (Acc⁶) are described. Boc-Aib-Acc⁶-NHMe · H₂O adopts a β-turn conformation in the solid state, stabilized by an intramolecular 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The backbone conformational angles (φ_Aib = – 50.3°, ψ_Aib = – 45.8°; φ_Acc6 = – 68.4°, ψ_Acc6 = – 15°) lie in between the values expected for ideal Type I or III β-turns. In Boc-Aib-Acc⁶-OMe, the Aib residue adopts a partially extended conformation (φ_Aib = – 62.2°, ψ_Aib = 143°) while the Acc⁶residue maintains a helical conformation (φ_Acc6 = 48°, ψ_Acc⁶= 42.6°). ¹H n.m.r. studies in CDCl₃ and (CD₃)₂SO suggest that Boc-Aib-Acc⁶-NHMe maintains the β-turn conformation in solution.     

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.     

Role of azaamino acid residue in β‐turn formation and stability in designed peptide

Abstract: The structural perturbation induced by C^αH→N^α exchange in azaamino acid‐containing peptides was predicted by ab initio calculation of the 6‐31G* and 3‐21G* levels. The global energy‐minimum conformations for model compounds, For‐azaXaa‐NH₂ (Xaa = Gly, Ala, Leu) appeared to be the β‐turn motif with a dihedral angle of φ = ± 90°, ψ = 0°. This suggests that incorporation of the azaXaa residue into the i + 2 position of designed peptides could stabilize the β‐turn structure. The model azaLeu‐containing peptide, Boc‐Phe‐azaLeu‐Ala‐OMe, which is predicted to adopt a β‐turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using ¹H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and IR spectroscopy defined the dihedral angles [ (φ_i+1, ψ_i+1) (φ_i+2, ψ_i+2)] of the Phe‐azaLeu fragment in the model peptide, Boc‐Phe‐azaLeu‐Ala‐OMe, as [(?59^°, 127^°) (107^°, ?4^°)]. This solution conformation supports a βII‐turn structural preference in azaLeu‐containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i + 2 position in synthetic peptides is expected to provide a stable β‐turn formation, and this could be utilized in the design of new peptidomimetics adopting a β‐turn scaffold.     

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.     

Non coded Cα,α-disubstituted amino acids

The crystal and molecular structure of the fully protected dipeptide Boc-Val-(S)-α-MeSer-OMe has been determined by X-ray diffraction techniques. Crystals grown from ethyl acetate/n-pentane mixtures are tetragonal, space group 14₁, with cell parameters at 295 K of a= 15.307(2), c= 18.937(10)Å, V = 4437.1 ų, M.W. = 332.40, Z = 8, D_m= 0.99 g/cm³ and D_x= 0.995 g/cm³. The structure was solved by application of direct methods and refined to an R value of 0.028 for 1773 reflections with I≥3σ(I) collected on a CAD-4 diffractometer. Both chiral centers have the (S) configuration. The dipeptide assumes in the solid state an S shape. The urethane moiety is in the cis conformation, while the amide bond is in the common trans conformation. The conformational angles φ₁, ψ₁ of the Val and φ₂, and ψ₂ of the (S)-αMeSer fall in the F region of the φ-ψ map. The isopropyl side chain of the Val residue has the (t, g^?) conformation, while the Ser side chain has a g⁺ conformation. The hydrogen bond donor groups are all involved in intermolecular H-bond interactions. Along the quaternary axis the dipeptide molecules are linked to each other with the formation of infinite rows.     

Molecular design of peptides

The peptide N-Boc-l -Phe-dehydro-Abu-NH-CH₃ was synthesized by the usual workup procedure. The crystals grown from methanol at 4°C belong to the space group P2₁2₁2₁ with a= 7.589(2), b= 13.690(4), c= 21.897(6) Å, Z= 4 and d_c= 1.149(5) g cm^?3 for C₁₉H₂₉N₃O₅·CH₃OH. The peptide crystals were highly sensitive to radiation. The final agreement factor R was 0.055 for 1109 observed reflections (I > 2σ) with data extending to a 2θ value of 103°. The methanol oxygen atom is split into two occupancies. Both sites are involved in identical hydrogen bonding. As a result of substitution of a dehydro-Abu residue at the (i+ 2) position the peptide adopts an ideal β-turn II′ conformation with torsion angles of corner residues as φ₁=63(1)°, ψ₁= - 127(1)°, φ₂= -66(1)° and ψ₂= - 10(1)°, and an intramolecular hydrogen bond N—H ? O of length 3.01(1) Å. This shows that the conformational constraints produced by dehydro-Abu are similar in nature to but different in magnitude than those produced by dehydro-Phe and dehydro-Leu. The methanol–peptide interactions show characteristic features of multiple hydrogen-bond formations involving polar sites of participating peptide and methanol molecules. The packing of the molecules in the unit cell is stabilized by interactions through methanol molecules with the help of several hydrogen bonds.     

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.     

Design of peptides: synthesis,crystal structure and molecular conformation of N-Boc-L-Val-δPhe-L-Ile-OCH3

The dehydro-peptide Boc-L-Val-δPhe-L-Ile-OCH₃ was synthesized by the azlactone method in the solution phase. The peptide crystallized from a methanol/dimethyl sulfoxide (95:5) mixture in space group P6₁, with a=b= 15.312(1), c= 22.164(5) Å. The structure was determined by direct methods and refined to an R value of 0.098 for 1589 observed reflections [I≥ 1.5 σ(I)]. The peptide adopts an S-shaped conformation with torsion angles: ø₁=-127(1), ψ₁= -44(1), ø₂, = 67(1), ψ₂, = 37(1), ø₃,=-82(1)°. The side-chain torsion angles in δPhe of X¹₂= 1(2), X^2.1₂= 7(2) and X_2.22 = 177(1)° indicate that the δPhe residue is essentially planar. In valyl residue the two side-chain torsion angles are X¹₁= -65(1) and X²₁= 177(1), whereas the torsion angles in Ile are X^1,1₃= 72(2), X^1,2₃= -159(2), X²₃= 150(2)°. This is the first peptide which does not adopt a folded conformation for a sequence with a δPhe at the (i+ 2) position. The molecular packing in the crystals is stabilized by several hydrogen bonds: N₁-H₁?O₁’= 2.77(1) Å, N₂-H₂?O₁’= 2.95(1) Å, N₃-H₃?O₂=2.85(1) Å and a possible weak interaction N₂-H₂?O₁’3.29(1) Å- within the columns of molecules along the c-axis and van der Waals forces between the columns. © Munksgaard 1996.     

Motifs and conformational analysis of amino acid residues adjoining β-turns in proteins

Using a data set of 250 non-homologous high-resolution globular proteins, a systematic analysis of the conformations that precede and succeed (positions i and i+3) the various classical β-turn types has been carried out. The collective conformation of a specific β-turn type, including the flanking positions, termed motif, has been studied. In all the four turn types, the majority of examples are preceded and succeeded by extended conformation. Some of the other observations are: (1) In a type I β-turn, Gly at position i+ 3 has a higher favorability to occur with positive ø and does not prefer the major motif βα_R-α_R-β. (2) The left-handed alpha;-helical conformation (alpha;_L) is not preferred at both the flanking positions for type I'and II β-turns, (3) The β–β motif is favourable for all the turn types and the motif β–α_L very highly favourable for type I. © Munksgaard 1996.     

Linear tripeptide conformation

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

Crystal structures of a nonapeptide helix containing α, α-di-n-butylglycine (Dbg), Boc-G1y-Dbg-Ala-Val-Ala-Leu-Aib-Val-Leu-OMe

Two crystal structures of a nonapeptide (anhydrous and hydrated) containing the amino acid residue α,α-di-n-butylglycyl, reveal a mixed 3₁₀-α-helical conformation. Residues 1-7 adopt φ, ψ values in the helical region, with Val(8) being appreciably distorted. The Dbg residue has φ, ψ values of -40, -37° and -46, -407° in the two crystals with the two butyl side chains mostly extended in each. Peptide molecules in the crystals pack into helical columns. The crystal parameters are: C₅₀ H₉₁ N₉ O₁₂, space group P2₁, with a= 9.789(1)Å;, b= 20.240(2) Å. c= 15.998(3) Å. β= 103.97(1): Z= 2, R=10.3% for 1945 data observed < 3σ(F) and C₅₀H₉₁N₉O₁₂· 3H₂O, space group P2₁ with a= 9.747(3)Å, b= 21.002(8) Å, c= 15.885(6) Å, β= 102.22(3). Z= 2. R=13.6% for 2535 data observed < 3σ(F) The observation of a helical conformation at Dbg suggests that the higher homologs in the α,α-dialkylated glycine series also have a tendency to stabilize peptide helices. © Munksgaard 1996.     

The pseudo-βI-turn

Synthesis and conformational analysis of three cyclic hexapeptides cyclo(-Gly¹-Pro²-Phe³-Val⁴-Xra⁵-Phe⁶), Xaa= Phe (I), D-Phe (II) and D-Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all ¹H and ¹³C resonances was achieved by homo- and heteronuclear 2D-NMR techniques (TOCSY, ROESY, HMQC, HMQC-TOCSY and HMBCS-270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo- and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS-270). For structural refinements restrained molecular dynamics (MD) simulations in vacuo and in DMSO were performed. Each peptide exhibits two conformations in DMSO solution due to cis-trans isomerism about the Gly-Pro peptide bond. Surprisingly the cis-Gly-Pro segment in the minor isomers is not involved in a βVI-turn, but forms a turn structure with cis-Gly-Pro in the i and i+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ-angles closely correspond to a βI-turn [Pro²:φ(i+ 1) -60°, ψ(i+ 1) -30° Phe³: φ(i+ 2) -100°, ψ(i+ 2) -50°]. Hence we call this structural element a pseudo-βI-turn. As expected, in the dominating all-trans isomers proline occupies the i+ 1 position of a standard βI-turn. Therefore, cis-trans isomerization of the Gly¹-Pro² amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality of the i+ 1 amino acid for both isomers (βI for Phe⁵, βII′ for D-Phe⁵ or D-Prp⁵).     

Crystal-state structural analysis of two γ-lactam-restricted analogs of Pro-Leu-Gly-NH2

The crystal structures of two analogs of Pro-Leu-Gly-NH, (1), containing a γ-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastere-omer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual “C₅” conformation [ψ₁=– 0.8(15)°] stabilized by a (peptide)N-H…N(amino) intramolecular H-bond [the N(3)…N(4) separation is 2.687(11)Å]. Conversely, the N,N′-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a β-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [φ= 57.4(4), ψ₂=– 129.9(3)°; ψ₃= - 92.3(4), ψ₃= 6.4(5)°] lie close to the values expected for the corner residues of an ideal type-II β-bend. A weak intramolecular 4 → 1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C=O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the ψ₁ torsion angle is 12.9(4)° and the intramolecular N(3)…N(4) separation is 2.321(4)Å.     

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.     

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°.     

Conformational investigation of α,β-dehydropeptides Part VI. Molecular and crystal structure of benzyloxycarbonylglycyl-(Z)-dehydrophenylalanine

The structure of a peptide containing C-terminal dehydrophenylalanine, Z-Gly-(Z)-δPhe (C₁₉H₁₈N₂O₅, MW = 354) was determined from single-crystal X-ray diffraction data. Needle-shaped crystals were grown from a 1:1 mixture of methanol-acetone in the monoclinic space group P2₁ with a= 14.717(4), b= 4.941(2), c= 12.073(4) Å, β= 103.72(4)?; V= 852.86(8) ų, Z= 2 and D_c= 1.32 g cm ^?3. The structure was solved by direct methods using SHELXS-86 and refined to a final R-index of 0.032 for 1714 observed reflections. The peptide adopts a conformation folded at the glycine residue, and principal torsion angles are ω₀= 167.6(2)?, pHGR;₁= -71.8(3)?, ψ₁= -31.6(4)?, ω_l= - 165.7(3)?, pHGR;₂= 65.6(4)?, ψ1/2 = -174.4(3)? and ψ2/2 = 5.2(4)?. Two intermolecular hydrogen bonds, N₁—H…O_o and O₂—H…O′₁, join the folded molecules into columns and link columns to each other, respectively. FTIR spectroscopy shows the presence of three hydrogen bonds. This third one has been interpreted as an intramolecular hydrogen bond of the N₂—H…N₁ type. © Munksgaard 1994.