Crystal and molecular structure of l-valyl-l-lysine hydrochloride

l -Valyl-l -lysine hydrochloride, C₁₁N₃O₃H₂₃ HCl, crystallizes in the monoclinic space group P2, with a = 5.438(5), b = 14.188(5), c = 9.521(5) Å, β= 95.38(2)° and Z = 2. The crystal structure, solved by direct methods, refined to R = 0.036, using full matrix least-squares method. The peptide exists in a zwitterionic form, with the N atom of the lysine side-chain protonated. The two γ-carbons of the valine side-chain have positional disorder, giving rise to two conformations, χ¹¹₁= -67.3 and 65.9°, one of which (65.9°) is sterically less favourable and has been found to be less popular amongst residues branching at β-C. The lysine side-chain has the geometry of g^? tgt, not seen in crystal structures of the dipeptides reported so far. Interestingly, χ³₂ (63.6°) of lysine side-chain has a gauche⁺ conformation unlike in most of the other structures, where it is trans. The neighbouring peptide molecules are hydrogen bonded in a head-to-tail fashion, a rather uncommon interaction in lysine peptide structures. The structure shows considerable similarity with that of l -Lys-l -Val HO in conformational angles and H-bond interactions [4].     

Conformation of arginine side chain in a mini peptide. Molecular structure of acetyl-l-arginine-ethylamide

The crystal structure of N-α-acetyl-l -arginine ethylamide perchlorate (molecular formula: C₁₀H₂₁N₅O₂ ± HClO₄) has been determined from X-ray diffraction data. This arginine derivative has the two charged ends substituted by peptide units and thus becomes representative of an arginyl residue in a protein. The crystals are orthorhombic, space group P2₁,2₁,2₁, a = 7.485 (2), b = 28.623 (5), c = 7.261 (3) Å, Z = 4. The structure was solved by direct methods and refined by full matrix least-squares using 559 reflections to an R = 0.052. The molecule shows two planar peptide units with φ and ø values in the β pleated sheet region. The side chain torsion angles are in trans conformation, except the χ₁, angle which is in the gauche(-) region. This observation further illustrates that this is one of the favoured side chain conformations of arginine, together with the all-trans conformation. Symmetric double hydrogen bonds are observed between the guanidinium group and perchlorate anions. The H(N) and oxygen atoms of the amide groups also form hydrogen bonds.     

Synthesis of partial sequences of ribosomal proteins and their derivatization with acryloyl residues

Peptide sequences B-X-B (B = Arg and/or Lys; X = Glu or Asp) are of considerable interest because of their possible interactions with ribosomal RNA. The syntheses of various protected peptides with the sequence Ala-B-X-B-Ala (X = Glu or Ala) and [Arg]_n-Pro (n = 1–3) are described. They are carried out in solution according to the conventional peptide synthesis method. The carbobenzoxy group is used for Nα-protection and the methyl group for the protection of the terminal carboxyl group. The side chains of Lys and Glu are respectively blocked with the tert.-butyloxycarbonyl and the tertiary butyl group and the guanidinic function of arginine with the NO₂-group. The intermediate peptides are purified either by extraction or by size exclusion chromatography. A specially adapted strategy of peptide synthesis allows removal of the amino terminal Cbo-group at the end of the synthesis and introduction of an acryloyl group. By radical copolymerization with cross-linking agents these acryloyl derivatives can be transferred into insoluble peptide gels suitable for affinity chromatography and for investigating peptide-oligonucleotide interactions. The isolation of the unprotected peptides Arg-Arg-Arg-Pro, Ala-Arg-Glu-Arg-Ala, Ala-Arg-Glu-Lys-Ala, Ala-Arg-Ala-Lys-Ala, Ala-Lys-Glu-Lys-Ala and their characterization using amino acid analysis, electrophoresis, and FAB-mass spectrometry is also reported.     

Crystal structure,conformation, and potential energy calculations the chemotactic peptide N- formyl-l-Met-l-Leu-l-Phe-OMe

The tripeptide N-formyl-L-Met-l -Leu-l -Phe-OMe (FMLP-OMe) crystallizes in the orthorhombic system, space group P 2₁2_l2₁, with the following unit-cell parameters: a = 21.727, b = 21.836, c = 5.133Å, Z = 4. The structure has been solved and refined to a final R of 0.068 for 1838 independent reflexions with I > 2σ(I). The peptide backbone is folded at the Leu residue (φ_L=?67.7,Ψ_L=?49.1°) without intramolecular hydrogen bonds. Considering each peptide plane, the Leu side-chain is oriented on the same side of that of the Phe residue and on the opposite side of that of the Met residue, respectively. The crystal conformation differs from all the other conformations proposed for FMLP-OMe and the anionic form of N-formyl-l -Met-l -Leu-l -Phe-OH (FMLP) in solution accounts for the amphiphilic character of the peptide, giving rise, through intermolecular hydrogen bonds, to a stacking of molecules which could be maintained in the aggregation states experimentally observed in solvents of low polarity. Intramolecular potential energy calculations have ben carried out in order to compare the energies of the various backbone conformers.     

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.     

Design of peptides with αβ-dehydro residues: Synthesis,crystal structure and molecular conformation of N-Boc-L-Ile-ΔPhe-L-Trp-OCH3

The dehydro-peptide Boc-L-Ile-ΔPhe-L-Trp-OCH₃ was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P2₁2₁2₁ with a = 10.777(2), b= 11.224(2), c= 26.627(10) Å. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [l≥ 2σ(l)].The peptide failed to adopt a folded conformation with backbone torsion angles: φ₁, = 90.8(8)°, ψ₁= -151.6(6)°, φ₂= 89.0(8)°, ψ₂= 15.9(9)°, φ₃= 165.7(7)°, ψ^T₃= -166.0(7)°. A general rule derived from earlier studies indicates that a three-peptide unit sequence with a ΔPhe at the (i+ 2) position adopts a β-turn II conformation. Because the branched β-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the ΔPhe residue differently to generate a unique set of conformations in such peptides. The presence of β-branched residues simultaneously at both (i+ 1) and (i+ 3) positions induces unfolded conformations in tetrapeptides, but a β-branched residue substituted only at (i+ 3) positron can not prevent the formation of a folded β-turn II conformation. On the other hand, the present structure shows that a β-branched residue substituted at the (i+ 1) position prevents the formation of a β-turn II conformation. These observations indicate that a β-branched residue at the (i+ 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i+ 3) position. This may be because of the trans disposition of the planar ΔPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N₂-H₂…O₂ (-x,y-1/2, -z+ 3/2) and N^ε1₃-H^ε1₃…O₁(-x,y -1/2, -z+ 3/2) hydrogen bonds.     

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.     

Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine‐containing fMLF analogs

Abstract: In order to explore the properties of chemotactic N‐formylpeptides containing isopeptide bonds within their backbones, a group of lysine‐containing analogs of the prototypical chemotactic tripeptide N‐formylmethionyl‐leucyl‐phenylalanine (fMLF) was synthesized. The new analogs were designed by adding to the HCO‐Met or Boc‐Met residue a dipeptide fragment made up of Lys and Phe residues joined through Lys N^α or N^ε bonds, in all possible combinations. Thus, the following six pairs of tripeptides were synthesized and examined for their bioactivity: RCO‐Met‐Lys(Z)‐Phe‐OMe ( 2a , b ), RCO‐Met‐Lys(Z‐Phe)‐OMe ( 3a , b ), Z‐Lys(RCO‐Met)‐Phe‐OMe ( 4a , b ), Z‐Phe‐Lys(RCO‐Met)‐OMe ( 5a , b ), RCO‐Met‐Phe‐Lys(Z)‐OMe ( 6a , b ) and Z‐Lys(RCO‐Met‐Phe)‐OMe ( 7a , b ), with R=OC(CH₃)₃ and R=H for compounds a and b , respectively. All the new models were characterized fully and their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils determined as agonists (compounds b ) and antagonists (compounds a ). All N‐formyl derivatives 2b ? 7b are less potent than fMLF‐OMe as chemoattractants, but compound 7b exhibits selective activity as superoxide anion producer. Derivatives 2a ? 7a do not show antagonistic activity towards fMLF induced chemotaxis and O₂^? production, however, all these compounds except 4a antagonize lysozyme release by 60%.     

Structure and conformation of peptides containing the sulfonamide junction II. Synthesis and conformation of cyclo[-MeTau-Phe-DPro-]

By applying the method of amino-acyl incorporation to sulfonamido peptides, cyclo(-MeTau-Phe-DPro-) 3 has been synthesized in high yield starting from Z-MeTau-Phe-Pro-OH. The crystal structure and the molecular conformation of 3 have been determined. Crystals are orthorhombic, s.g. P2₁2₁2₁, with a = 5.454, b = 13.486, c = 24.025 Å. The structure has been solved by direct methods and refined to R = 0.039 for 1974 reflections with I > 1.50 σ(I). The 10-membered cyclopeptide adopts a backbone conformation in the crystals characterized by Phe-DPro and DPro-MeTau peptide bonds in trans and cis conformation, respectively. Both the peptide bonds deviate significantly from planarity and the corresponding |δω| values are ca. 12°. The sulfonamide SO₂NH junction adopts a cisoidal conformation with a C^α₁- S₁-N₂- C₂^α torsion angle of 70.8°. ¹³C n.m.r. data show that the trans geometry at the Phe-DPro junction found in the crystals is retained in DMSO solution. The 10-membered ring of 3 is characterized by a pseudo mirror-plane passing through the Phe nitrogen and the DPrO carbonylic carbon. The DPrO ring adopts a half-chair conformation. The Phe side chain conformation corresponds to the statistically most favored g^? rotamer (χ¹= - 68.6°). The crystal packing is characterized by a weak intermolecular hydrogen bond between the NH group and the MeTau O₁’ oxygen.     

X-Ray structure of Tyr-D-Tic-Phe-Phe-NH2 (D-TIPP-NH2), a highly potent μ-receptor selective opioid agonist. Comparisons with proposed model structures

Tyr-D-Tic-Phe-Phe-NH₂ (D-TIPP), a linear tetrapeptide containing the conformationally restricted Tic residue (tetrahydroisoquinoline-3-carboxylic acid), is an opioid agonist which exhibits high affinity and selectivity for the μ-receptor. Its conformational features have been studied using a combination of solid-state (X-ray) and modeling (molecular mechanics and Monte Carlo simulations) methods. The results of the X-ray study showed two distinct conformers for D-TIPP, with the main differences lying in the orientation of the Tyr side-chain and the presence of both D-Tic(+) and D-Tic(—) conformations for the D-Tic residue. The peptide backbone is folded and stablized by the formation of one intramolecular hydrogen bond. The modeling results also indicated a folded backbone for the peptide and both cis and trans conformers for the D-Tic residue are found in the lowest-energy structures. Comparison of the X-ray and modeling results shows many similarities especially around the D-Tic residue. © Munksgaard 1997.     

Heterochiral N-formyl methionyl peptides

Crystal and molecular structures for the heterochiral sequence N-formyl-l -methionine-d -phenylalanine, 1, and its tertiary butyl ester, 2, are reported. The solid-state peptide conformation is compared to that observed in solution by n.m.r. techniques. For N-f-Met-d -Phe, 1, the crystal was orthorhombic, space group P2₁ 2₁2₁ with a cell of dimensions a = 5.061(3), b = 16.575(5) and c = 19.656(6) Å at ambient temperature of 293K; V = 1649(2)ų, Z = 4, D_m= 1.31(2)gcm^?3, D_x= 1.307gcm^?3, μ(Mokx) = 2.047cm^?1. For N-f-Met-d -Phe-OtBu. 2, the crystal was monoclinic, space group P2₁ with a cell of dimensions a = 9.963(2), b = 11.147(2), c = 19.166(3)Å. β= 102.31(1) at 273K; V = 2080(2) ų Z = 4, D_m= 1.22(2)gcm^?3, D_x= 1.215gcm^?3μ(MoKx) = 1.714cm^?1. The structures were solved from diffractometer data and refined to conventional final R = 0.046, R_w= 0.053 for F-Met-d -Phe (1301 observations. I ≥ 3σ(I)) and to R = 0.056, R_w= 0.064 for the t-butylester (2411 observations. I ≥ 3σ(I)). The l-d acid, 1, crystallizes in an extended β-sheet conformation with trans-planar peptide bond; the principal torsion angle values are φ₁=– 141.2(4).Ψ₁= 149.6(4)³, φ₂= 157.4(4)°. The methionine side chain adopts a common coiled conformation with x¹₁= - 58.0(5).x²¹= 175.1(4), x³₁= 76.5(5). The Phe side chain adopts the statistically least favored g orientation in contrast to the most populated rotamer in solution. The crystal structure is composed of parallel β-sheets held together by four weak intermolecular contacts including two C-H O contacts from the alpha carbons to the formyl and peptide carbonyl oxygens. Sheet layers are joined in a head-to-tail fashion through a very short (2.569(4) Å) contact between the carboxyl OH and the formyl oxygen and may be further stabilized by a C-H—O interaction between the formyl proton and the carboxyl OH. Two crystallographically independent molecules are observed in the crystal structure of N-f-l -Met-d -Phe-OtBu, 2. These are distinct conformational isomers differing principally at both the N and C termini. Particularly noteworthy is the synplanar orientation of the ester C = O with respect to the peptide nitrogen in molecule A. which contrasts to the antiplanar orientation in molecule B. Additionally, the formyl group is coiled more towards the C-terminus in molecule B. Principal torsion angles are φ₁(A) = - 120.6(5), Ψ₁(A) = 102.0(6)°, φ₂(A) = 128.1(6), φ₁(B) = - 94.6(5), Ψ₁(B) = 91.9(6)°. 121.7(6)°. The peptide bond is trans-planar in both molecules. Side chain dispositions are essentially identical in both structures. The Met side chain adopts the zig-zag trans-planar conformation while the Phe residue adopts an orientation near + 60° in agreement with rotamer populations observed by solution n.m.r. Typical peptide intermolecular H-bonding is observed in the ester crystal structure; both the peptide and formyl groups participate in the proposed H-bonding scheme.     

Crystal and molecular structure of L-lysyl-L-valine hydrochloride – a new lysine conformation

Thin plates of L-lysyl-L-valine hydrochloride (C₁₁H₂₄N₃O₃Cl) were obtained using the vapour diffusion technique and analysed by X-ray diffraction. The unit cell is orthorhombic, space group P2₁2₁2₁, a = 5.465(6)Å, b = 19.657(4) Å, c = 13.522(2) Å, V = 1452.6(2.1) ų and Z = 4. The structure was solved by direct methods and refined to an agreement factor of 6.7% for 939 reflections with I > 3 σ(I). The lysine side chain conformation (g^- g^- tt) has never been found in peptide crystal structures, although it has been reported to occur in proteins. A network of hydrogen bonds between peptide molecules spreads along the a and c directions while no direct bonds are observed to occur between peptides along the b axis direction. This asymmetric pattern of interactions correlates with the crystal morphology.     

Peptides containing the sulfonamide transition-state isostere: synthesis and structure of N-acetyl-tauryl-l-proline methylamide

The structure of the sulfonamide isostere-containing peptide N-acetyl-tauryl-proline methylamide 4 was compared to information on the structure of the peptide N-acetyl-β-alanyl-proline methylamide 6. NMR measurements of the β-alanine containing peptide 6 showed the presence of two conformations due to cis/trans isomerism of the β-Ala-Pro amide bond, whereas the sulfonamide-containing peptide 4 appeared in only one conformation. The crystal structure of N-acetyl-tauryl-proline methylamide 4 gave additional evidence for the absence of cis/trans isomerism. The crystals are orthorhombic, space group P2₁2₁2₁, Z= 4, F(000) = 592, a= 7.5919(3), b= 10.3822(2), c= 17.1908(7) Å, V= 1354.99(8) ų, D_x= 1.359 g cm^?3. The oxygen atoms connected to the sulfur take positions similar to both the cis and trans positions of the carbonyl oxygen of an amide. Consequently the tauryl part is placed perpendicular to the proline α-C-C(O) bond, giving it an extended conformation in contrast to the cis/trans isomers of N-acetyl-β-alanyl-proline methylamide 6. © Munksgaard 1995.     

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.     

Structure and conformation of peptides containing the sulphonamide junction

N-acetyl-tauryl-l -phenylalanine methyl ester 1 has been synthesized. The crystal structure and molecular conformation of 1 have been determined. Crystals are monoclinic, space group P2₁ with a = 5.088(2), b = 17.112(17), c = 9.581(6) Å, β= 92.34(4)^M-0, Z = 2. The structure has been solved by direct methods and refined to R = 0.043 for 2279 reflections with I < 1.5σ(I). The sulphonamide junction maintains the peptide backbone folded with Tau and Phe C^α atoms in a cisoidal arrangement, the torsion angle around the S-N bond being 65.4^M-0. In this conformation the p-orbital of the sulphonamide nitrogen lies in the region of the plane bisecting the O-S-O angle, thus favouring dα-pα interactions between nitrogen and sulphur atoms. The S-N bond with a length of 1.618 Å has significant α-bond character. The CO-NH is planar and adopts trans conformation. The Tau residue is extended with the Tau-C^α₁-C^β_a bond anti-periplanar to the S-N bond. The Phe side chain conformation corresponds to the statistically most favoured g^- rotamer and exhibits a χ¹ torsion angle of –67.5^M-0. The packing is characterized by intermolecular H-bonds which the Tau and Phe NH groups form with the acetyl carbonyl and one of the two sulphonamide oxygens, respectively.     

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.     

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.     

Crystal structure and conformation of polypeptides: L-leucylglycylglycylglycine

Crystals of L-leucylglycylglycylglycine, LGGG (C₁₂H₂₂N₄O₅), grown from an ethanol-water solution, are orthorhombic, space groups P2₁2₁2₁, with unit cell dimensions (at 22 ± 3°) a = 9.337(1), b = 10.995(1), c = 15.235(1)Å, v = 1563.4 ų, Z = 4 with a density of D_obs= 1.29 g-cm^-3 and D_calc= 1.279 g°cm^-3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.029 for 1018 reflections with I ± 2s?. The molecule exists as a zwitterion in the crystal. The trans peptide backbone takes up a folded conformation at the middle glycylglycyl link accompanied by a significant nonplanarity up to Δω of 8° at the middle peptide and is relatively more extended at the two ends. The molecules are linked together intermolecularly in an infinite sequence of head to tail 1–4′ hydrogen bonds, as is typical of charged peptides. It is interesting to note that while glycylglycylglycine takes up an extended β-sheet conformation, addition of Leu to the N-terminal results in a bent conformation.     

Crystal structure and conformation of l-pyroglutamyl-l-alanine

Crystals of the dipeptide, pyroglutamyl-alanine (C₈H₁₂N₂O₄) grown from aqueous methanol are monoclin-ic, space group P2₁ with the following cell parameters: a = 4.863(2), b = 16.069(1), c = 6.534(2)Å and β= 109.9(2)°, V = 480.0ų, M_r= 200.2, D_c= 1.385 g cm^?3, and Z = 2. The crystal structure was solved by the application of direct methods and refined to an R value of 0.044 for 699 reflections with I > 2σ. The amide of the pyroglutamyl side chain is cis, ω₁= 2.6(7)°; the peptide unit is trans and appreciably non-planar (ω₂= 167.4(5)°). The backbone torsional angles are: Ψ₁= 166.1(5), φ₂=?90.3(6), and Ψ₂=?22.4(6)°. This structure contains a short (2.551(5)Å) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most acyl amino acids and acyl peptides.     

Influence of hydrophobic interactions on the conformational adaptability of the β‐Ala residue

Abstract: The chemical synthesis and X‐ray crystal structure analysis of a model peptide incorporating a conformationally flexible β‐Ala residue: Boc‐β‐Ala‐Pda, 1 (C₂₃H₄₆N₂O₃: molecular weight = 398.62) have been described. The peptide crystallized in the crystal system triclinic with space group P2₁: a = 5.116(3) Å, b = 5.6770(10) Å, c = 21.744(5) Å; α = 87.45°, β = 86.87°, γ = 90.0°; Z = 1. An attractive feature of the crystal molecular structure of 1 is the induction of a reasonably extended backbone conformation of the β‐Ala moiety, i.e. the torsion angles φ ≈ ?115°, µ ≈ 173° and ψ ≈ 122°, correspond to skew^?, trans and skew⁺ conformation, respectively, by an unbranched hydrophobic alkyl chain, Pda, which prefers an all‐anti orientation (θ₁ ≈ ?153°, θ₂ ≈ … θ₁₄ ≈ ±178°). The observation is remarkable because, systematic conformational investigations of short linear β‐Ala peptides of the type Boc‐β‐Ala‐Xaa‐OCH₃ (Xaa = Aib or Acc⁶) have shown that the chemical and stereochemical characters of the neighboring moieties may be critical in dictating the overall folded and/or unfolded conformational features of the β‐Ala residue. The overall conformation of 1 is typical of a ‘bar’. It appears convincing that, in addition to a number of hydrophobic contacts between the parallel arranged molecules, an array of conventional N‐H…O=C intermolecular H‐bonding interactions stabilize the crystal molecular structure. Moreover, the resulting 14‐membered pseudo‐ring motif, generated by the amide–amide interactions between the adjacent molecules, is completely devoid of nonconventional C?H…O interaction. The potentials of the conformational adaptation of the β‐Ala residue, to influence and stabilize different structural characteristics have been highlighted.