Molecular dynamics studies of side chain effect on the beta-1,3-D-glucan triple helix in aqueous solution

beta-1,3-D-glucans have been isolated from fungi as right-handed 6(1) triple helices. They are categorized by the side chains bound to the main triple helix through beta-(1-->6)-D-glycosyl linkage. Indeed, since a glucose-based side chain is water soluble, the presence and frequency of glucose-based side chains give rise to significant variation in the physical properties of the glucan family. Curdlan has no side chains and self-assembles to form an water-insoluble triple helical structure, while schizophyllan, which has a 1,6-D-glucose side chain on every third glucose unit along the main chain, is completely water soluble. A thermal fluctuation in the optical rotatory dispersion is observed for the side chain, indicating probable co-operative interaction between the side chains and water molecules. This paper documents molecular dynamics simulations in aqueous solution for three models of the beta-1,3-D-glucan series: curdlan (no side chain), schizophyllan (a beta-(1-->6)-D-glycosyl side-chain at every third position), and a hypothetical triple helix with a side chain at every sixth main-chain glucose unit. A decrease was observed in the helical pitch as the population of the side chain increased. Two types of hydrogen bonding via water molecules, the side chain/main chain and the side chain/side chain hydrogen bonding, play an important role in determination of the triple helix conformation. The formation of a one-dimensional cavity of diameter about 3.5 A was observed in the schizophyllan triple helix, while curdlan showed no such cavity. The side chain/side chain hydrogen bonding in schizophyllan and the hypothetical beta-1,3-D-glucan triple helix could cause the tilt of the main-chain glucose residues to the helix.     

Secondary and tertiary structure of the A-state of cytochrome c from resonance Raman spectroscopy.

Ferricytochrome c can be converted to the partially folded A-state at pH 2.2 in the presence of 1.5 M NaCl. The structure of the A-state has been studied in comparison with the native and unfolded states, using resonance Raman spectroscopy with visible and ultraviolet excitation wavelengths. Spectra obtained with 200 nm excitation show a decrease in amide II intensity consistent with loss of structure for the 50s and 70s helices. The 230-nm spectra contain information on vibrational modes of the single Trp 59 side chain and the four tyrosine side chains (Tyr 48, 67, 74, and 97). The Trp 59 modes indicate that the side chain remains in a hydrophobic environment but loses its tertiary hydrogen bond and is rotationally disordered. The tyrosine modes Y8b and Y9a show disruption of tertiary hydrogen bonding for the Tyr 48, 67, and 74 side chains. The high-wavenumber region of the 406.7-nm resonance Raman spectrum reveals a mixed spin heme iron atom, which arises from axial coordination to His 18 and a water molecule. The low-frequency spectral region reports on heme distortions and indicates a reduced degree of interaction between the heme and the polypeptide chain. A structural model for the A-state is proposed in which a folded protein subdomain, consisting of the heme and the N-terminal, C-terminal, and 60s helices, is stabilized through nonbonding interactions between helices and with the heme.     

The crystal and molecular structure of VH amylose by electron diffraction analysis

The crystal and molecular structures of VH amylose were determined by a constrained linked-atom least-squares refinement, utilizing intensities measured from electron diffraction patterns and stereochemical restraints. Hexagonal platelet single crystals were grown from dilute aqueous ethanol solution and their electron diffraction diagrams analysed. These data indicated that the amylose chains were crystallized in a hexagonal lattice with a = b = 13.65 A, c (chain axis) = 8.05 A and space group P6(5)22. The best model obtained using the base plane data coupled with a stereochemical refinement yielded R = 0.24 (R' = 0.25). It corresponded to a system of left-handed 6-fold helices packed on an hexagonal net but with statistically random up/down chain disorder. A column of six water molecules was present within each helical repeat. Additionally, the gap between each pair of adjacent helices was bridged by two water molecules positioned so as to allow hydrogen bonding with chains of either sense. This proposed crystal structure differs somewhat from previous reports which invoked orthorhombic lattices and requires a regularly alternating arrangement of up and down chains to account for the intensity. Suggestions are made to account for these differences.     

A rare polyglycine type II‐like helix motif in naturally occurring proteins

Common structural elements in proteins such as α‐helices or β‐sheets are characterized by uniformly repeating, energetically favorable main chain conformations which additionally exhibit a completely saturated hydrogen‐bonding network of the main chain NH and CO groups. Although polyproline or polyglycine type II helices (PP_II or PG_II) are frequently found in proteins, they are not considered as equivalent secondary structure elements because they do not form a similar self‐contained hydrogen‐bonding network of the main chain atoms. In this context our finding of an unusual motif of glycine‐rich PG_II‐like helices in the structure of the acetophenone carboxylase core complex is of relevance. These PG_II‐like helices form hexagonal bundles which appear to fulfill the criterion of a (largely) saturated hydrogen‐bonding network of the main‐chain groups and therefore may be regarded in this sense as a new secondary structure element. It consists of a central PG_II‐like helix surrounded by six nearly parallel PG_II‐like helices in a hexagonal array, plus an additional PG_II‐like helix extending the array outwards. Very related structural elements have previously been found in synthetic polyglycine fibers. In both cases, all main chain NH and CO groups of the central PG_II‐helix are saturated by either intra‐ or intermolecular hydrogen‐bonds, resulting in a self‐contained hydrogen‐bonding network. Similar, but incomplete PG_II‐helix patterns were also previously identified in a GTP‐binding protein and an antifreeze protein.     

Helix packing of leucine-rich peptides: a parallel leucine ladder in the structure of Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe.

The packing of peptide helices in crystals of the leucine-rich decapeptide Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe provides an example of ladder-like leucylleucyl interactions between neighboring molecules. The peptide molecule forms a helix with five 5----1 hydrogen bonds and two 4----1 hydrogen bonds near the C terminus. Three head-to-tail NH ... O = C hydrogen bonds between helices form continuous columns of helices in the crystal. The helicial columns associate in an antiparallel fashion, except for the association of Leu ... Leu side chains, which occurs along the diagonal of the cell where the peptide helices are parallel. The peptide, with formula C56H102N10O13, crystallizes in space group P2(1)2(1)2(1) with Z = 4 and cell parameters a = 16.774(3) A, b = 20.032(3) A and c = 20.117(3) A; overall agreement factor R = 10.7% for 2014 data with magnitude of F(obs) greater than 3 sigma (F); resolution 1.0 A.     

An asymmetric conformation of 1,3,5-benzene tricarbonyl [Aib4OMe]3.

Molecules of 1,3,5-benzene tricarbonyl [Aib(4)OMe](3) do not possess any internal symmetry, neither exact nor approximate, in the crystalline state. The Aib(4)OMe moieties each form a 3(10)-helix with an appropriate pair of hydrogen bonds but the sense of rotation is right-handed for two of the helices and left-handed for the third one. The helices are not evenly positioned around the benzene ring, and their helix axes are inclined toward one side of the plane of the benzene ring, giving the molecule the shape of a shallow bowl with an irregular periphery. The molecules are largely surrounded by water and dimethyl sulfoxide (DMSO) solvent molecules that form hydrogen bonds with the CO and NH moieties that protrude from the surfaces of the peptide molecule. The space group is Cc with a = 23.618(4) A, b = 19.708(6) A, c = 17.939(7) A and beta = 100.09(3) degrees.     

Synthesis, crystal structure and molecular conformation of N-Ac-dehydro-Phe-L-Val-OH.

The peptide N-Ac-dehydro-Phe-L-Val-OH (C16H20N2O4) was synthesized by the usual workup procedure. The peptide crystallizes from its solution in acetonitrile at 4 degrees in hexagonal space group P6(5) with a = b = 11.874(2)A, c = 21.856(9) A, V = 2668(1) A3, Z = 6, dm = 1.151(3) g cm-3, dc = 1.136(4) g cm-3, CuK alpha = 1.5418 A, mu = 0.641 mm-1, F(000) = 972, T = 293 K. The structure was solved by direct methods and refined by least-squares procedure to an R value of 0.074 for 1922 observed reflections. In the dehydro-residue, the C1 alpha-C1 beta distance is 1.35(1) A while the bond angle C1 alpha-C1 beta-C1 gamma is 131.2(9) degrees. The backbone torsion angles are: omega 0 = 172(1) degrees, phi 1 = -60(2) degrees, psi 1 = -31(2) degrees, omega 1 = -179(1) degrees, phi 2 = 59(2) degrees. These values suggest that the peptide tends to adopt an alternating right-handed and left-handed helical conformation. The side chain torsion angles are: chi 1(1) = -6(2) degrees, chi 1(2.1) = -1(2) degrees, chi 1(2.2) = -178(2) degrees, chi 2(1.1) = 63(2) degrees and chi 2(1.2) = -173(1) degrees. These values show that the side chain of dehydro-Phe is planar whereas the valyl side chain adopts a sterically most preferred conformation. The molecules, linked by intermolecular hydrogen bonds and van der Waals forces, are arranged in helices along the c-axis. The helices are held side-by-side by van der Waals contacts.     

Short hydrogen bonds in proteins

Short hydrogen bonds are present in many chemical and biological systems. It is well known that these short hydrogen bonds are found in the active site of enzymes and aid enzyme catalysis. This study aims to systematically characterize all short hydrogen bonds from a nonredundant dataset of protein structures. The study has revealed that short hydrogen bonds are commonly found in proteins and are widely present in different regions of the protein chain, such as the backbone or side chain, and in different secondary structural regions such as helices, strands and turns. The frequency of occurrence of donors and acceptors from the charged side chains as well as from the neutral backbone atoms is equally high. This suggests that short hydrogen bonds in proteins occur either due to increased strength or due to geometrical constraints and this has been illustrated from several examples.     

Double helix formation in α‐peptides: a theoretical study

A complete overview on all possible hydrogen bonding patterns of double helices with antiparallel and parallel strand orientation in α‐peptide sequences is provided on the basis of ab initio molecular orbital theory. The most stable representatives belong to the group of antiparallel helices. The study on side chain influence shows that these double helices can only be realized if the strands are composed of L ‐ and D ‐amino acids in alternate order. The stability of the double helices is compared with that of competing single‐stranded helices. The data contribute to an understanding of secondary structure formation in peptides and provide a basis for a rational design of membrane channels. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Alpha helix capping in synthetic model peptides by reciprocal side chain–main chain interactions: Evidence for an N terminal “capping box”

A significant fraction of the amino acids in proteins are alpha helical in conformation. Alpha helices in globular proteins are short, with an average length of about twelve residues, so that residues at the ends of helices make up an important fraction of all helical residues. In the middle of a helix, H-bonds connect the NH and CO groups of each residue to partners four residues along the chain. At the ends of a helix, the H-bond potential of the main chain remains unfulfilled, and helix capping interactions involving bonds from polar side chains to the NH or CO of the backbone have been proposed and detected. In a study of synthetic helical peptides, we have found that the sequence Ser-Glu-Asp-Glu stabilizes the alpha helix in a series of helical peptides with consensus sequences. Following the report by Harper and Rose, which identifies SerXaaXaaGlu as a member of a class of common motifs at the N termini of alpha helices in proteins that they refer to as “capping boxes,” we have reexamined the side chain–main chain interactions in a varient sequence using ¹H NMR, and find that the postulated reciprocal side chain-backbone bonding between the first Ser and last Glu side chains and their peptide NH partners can be resolved: Deletion of two residues N terminal to the Ser-Glu-Asp-Glu sequence in these peptides has no effect on the initiation of helical structure, as defined by two-dimensional (2D) NMR experiments on this variant. Thus the capping box sequence Ser-Glu-Asp-Glu inhibits N terminal fraying of the N terminus of alpha helix in these peptides, and shows the side chain–main chain interactions proposed by Harper and Rose. It thus acts as a helix initiating signal. Since normal a helix cannot propagate beyond the N terminus of this structure, the box acts as a termination signal in this direction as well. © 1994 John Wiley & Sons, Inc.     

Propagating structural perturbation inside bacteriorhodopsin: crystal structures of the M state and the D96A and T46V mutants

The X-ray diffraction structure of the non-illuminated D96A bacteriorhodopsin mutant reveals structural changes as far away as 15 A from residue 96, at the retinal, Trp-182, Ala-215, and waters 501, 402, and 401. The Asp-to-Ala side-chain replacement breaks its hydrogen bond with Thr-46, and the resulting separation of the cytoplasmic ends of helices B and C is communicated to the retinal region through a chain of covalent and hydrogen bonds. The unexpected long-range consequences of the D96A mutation include breaking the hydrogen bond between O of Ala-215 and water 501 and the formation of a new hydrogen bond between water molecules 401 and 402 in the extracellular region. Because in the T46V mutant a new water molecule appears at Asp-96 and its hydrogen-bond to Ile-45 replaces Thr-46 as its link to helix B, the separation of helices B and C is smaller than that in D96A, and there are no atomic displacements elsewhere in the protein. Propagation of conformational changes along the chain between the retinal and Thr-46 had been observed earlier in the crystal structures of the D96N and E204Q mutants but in the trapped M state. Consistent with the perturbation of the retinal region in D96A, little change of the Thr-46 region occurs between the non-illuminated and M states of this mutant. It appears that a local perturbation can propagate along a track in both directions between the retinal and the Asp-96/Thr-46 pair, either from photoisomerization of the retinal in the wild-type protein in one case or from the D96A mutation in the other.     

The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition.

The virally encoded 3C proteinases of picornaviruses process the polyprotein produced by the translation of polycistronic viral mRNA. The X-ray crystallographic structure of a catalytically active mutant of the hepatitis A virus (HAV) 3C proteinase (C24S) has been determined. Crystals of this mutant of HAV 3C are triclinic with unit cell dimensions a = 53.6 A, b = 53.5 A, c = 53.2 A, alpha = 99.1 degrees, beta = 129.0 degrees, and gamma = 103.3 degrees. There are two molecules of HAV 3C in the unit cell of this crystal form. The structure has been refined to an R factor of 0.211 (Rfree = 0.265) at 2.0-A resolution. Both molecules fold into the characteristic two-domain structure of the chymotrypsin-like serine proteinases. The active-site and substrate-binding regions are located in a surface groove between the two beta-barrel domains. The catalytic Cys 172 S(gamma) and His 44 N(epsilon2) are separated by 3.9 A; the oxyanion hole adopts the same conformation as that seen in the serine proteinases. The side chain of Asp 84, the residue expected to form the third member of the catalytic triad, is pointed away from the side chain of His 44 and is locked in an ion pair interaction with the epsilon-amino group of Lys 202. A water molecule is hydrogen bonded to His 44 N(delta1). The side-chain phenolic hydroxyl group of Tyr 143 is close to this water and to His 44 N(delta1) and may be negatively charged. The glutamine specificity for P1 residues of substrate cleavage sites is attributed to the presence of a highly conserved His 191 in the S1 pocket. A very unusual environment of two water molecules and a buried glutamate contribute to the imidazole tautomer believed to be important in the P1 specificity. HAV 3C proteinase has the conserved RNA recognition sequence KFRDI located in the interdomain connection loop on the side of the molecule diametrically opposite the proteolytic site. This segment of polypeptide is located between the N- and C-terminal helices, and its conformation results in the formation of a well-defined surface with a strongly charged electrostatic potential. Presumably, this surface of HAV 3C participates in the recognition of the 5' and 3' nontranslated regions of the RNA genome during viral replication.     

The 2.6-A crystal structure of Pseudomonas putida cytochrome P-450

The crystal structure of Pseudomonas putida cytochrome P-450cam in the ferric, camphor bound form has been determined and partially refined to R = 0.23 at 2.6 A. The single 414 amino acid polypeptide chain (Mr = 45,000) approximates a triangular prism with a maximum dimension of approximately 60 A and a minimum of approximately 30 A. Twelve helical segments (A through L) account for approximately 40% of the structure while antiparallel beta pairs account for only approximately 10%. The unexposed iron protoporphyrin IX is sandwiched between two parallel helices designated the proximal and distal helices. The heme iron atom is pentacoordinate with the axial sulfur ligand provided by Cys 357 which extends from the N-terminal end of the proximal (L) helix. A substrate molecule, 2-bornanone (camphor), is buried in an internal pocket just above the heme distal surface adjacent to the oxygen binding site. The substrate molecule is held in place by a hydrogen bond between the side chain hydroxyl group of Tyr 96 and the camphor carbonyl oxygen atom in addition to complementary hydrophobic contacts between the camphor molecule and neighboring aliphatic and aromatic residues. The camphor is oriented such that the exo-surface of C5 would contact an iron bound, "activated" oxygen atom for stereoselective hydroxylation.     

New type of helix and 2(7) ribbon structure formation in poly DeltaLeu peptides: construction of a single-handed template

alpha,beta-Dehydroamino acid residues due to the presence of Calpha = Cbeta double bond influences the main chain and the side chain conformations. These residues have interesting chemical features including the increased resistance to enzymatic degradation. The chain length dependent conformational behavior of poly alpha,beta-dehydroleucine (DeltaLeu) peptides in both the pure forms Z and E and their various combinations like alternate ZE/EZ etc. have been investigated by using quantum mechanical method PCILO (perturbative configuration interaction of localized orbitals). The conformational states in alternate Z and E forms, with Phi, Psi values of -10 degrees , 105 degrees /1 degrees , -88 degrees for Z form and 35 degrees , 22 degrees /-34 degrees , -27 degrees for the E form are found to be the most stable and degenerate than the states in pure Z and E forms and the EZ form etc. The repeated Phi, Psi values give rise to altogether new types of left and right handed helices, and their stability increases with increasing chain length. These structures are stabilized by intramolecular hydrogen bonding, carbonyl-carbonyl interactions and hydrophobic interactions between the side chains of DeltaZLeu and DeltaELeu residues. The 2(7) ribbon structure (seven-membered hydrogen-bonded ring involving two consecutive amino acid residues) is found to be most stable and degenerate in the pentapeptide Ac-DeltaELeu5-NHMe, due to the formation of maximum hydrogen bonds. A right-handed template from achiral DeltaLeu peptides has been achieved by incorporating L-Leu at the C-terminal or D-Leu at the N-terminal.     

Effect of calcium ions on the organization of iota-carrageenan helices: an X-ray investigation

X-ray fiber diffraction analysis confirms that calcium iota-carrageenan forms a threefold, right-handed, half-staggered, parallel, double helix of pitch 26.42 A stabilized by interchain hydrogen bonds. According to the detailed structural results, three helices are packed in a trigonal unit cell (a=23.61 and c=13.21 A). Strong interactions between the sulfate groups of neighboring helices, mediated by calcium ions and water molecules, are responsible for stabilizing the three-dimensional structure.     

Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate.

The structure of rat intestinal fatty acid binding protein (I-FABP) with bound oleate (C18:1) has been refined with x-ray diffraction data to a resolution of 1.75 A. The protein contains 10 anti-parallel beta strands composed of 99 residues and 2 short helices of 14 residues. Oleate is located in the interior of the protein in a bent conformation with C1-C12 more ordered than C13-C18. Two of the eight ordered waters in I-FABP:oleate are part of a hydrogen bond network that includes the carboxylate of oleate, the guanidinium group of Arg106, the nitrogen of the indole group of Trp82, and the side chain of Gln115. Most of the methylenes of bound oleate reside in a crevice formed by hydrophobic and aromatic side chains. Tyr70 and Tyr117 envelop the acyl chain from C3 to C8 forming contacts with both the convex and concave faces of its van der Waals surface. The hydroxyls of each phenolic side chain hydrogen bond to ordered water molecules. Two ordered waters make van der Waals contact with the concave face of the bound fatty acid. The omega-terminal methyl of oleate is oriented so that it points toward the center of the benzene of Phe55 allowing it to form van der Waals interactions with its component methylenes. Comparison of the structure of I-FABP:oleate with a recently refined 1.19-A model of apoI-FABP and an earlier 2.0-A model of I-FABP:palmitate revealed a remarkable degree of similarity in the positions of their main chain and side chain atoms and in the conformations of the bound oleate and palmitate. The principal differences were confined to a few discrete regions of the protein. The helical domain, the type I turn between beta strands C and D, and the ring of Phe55 together form a solvent-accessible portal to the interior of the protein. They are repositioned in I-FABP:oleate (and I-FABP:palmitate) so that the binding cavity is even more accessible to solvent and its volume is increased. The side chain of Phe55 which shows discrete disorder in the apoprotein functions as an omega-terminal "sensing device": moving progressively outward toward the surface as the chain length of the bound fatty acid increases by 2 methylenes. Tyr70 and Tyr117 which also show discrete disorder in the apoprotein structure due to rotation around their C alpha-C beta bonds, are stabilized in a single, well ordered position in the holoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hydrogen bonding in a model bacteriochlorophyll-binding site drives assembly of light harvesting complex

In this study, the contribution of intramembrane hydrogen bonding at the interface between polypeptide and cofactor is explored in the native lipid environment by use of model bacteriochlorophyll proteins. In the peripheral antenna complex, LH2, large portions of the transmembrane helices, which make up the dimeric bacteriochlorophyll-binding site, are replaced by simplified, alternating alanine-leucine stretches. Replacement of either one of the two helices with the helices containing the model sequence at a time results in the assembly of complexes with nearly native light harvesting properties. In contrast, replacement of both helices results in the loss of antenna complexes from the membrane. The assembly of such doubly modified complexes is restored by a single intramembrane serine residue at position -4 relative to the liganding histidine of the alpha-subunit. In situ analysis of the spectral properties in a series of site-directed mutants reveals a critical dependence of the model complex assembly on the side chain of the residue at this position in the helix. A hydrogen bond between the hydroxy group of the serine and the 13(1) keto group of one of the central bacteriochlorophylls of the complexes is identified by Raman spectroscopy in the model antenna complex containing one of the alanine-leucine helices. The additional OH group of the serine residue, which participates in hydrogen bonding, increases the thermal stability of the model complexes in the native membrane. Intramembrane hydrogen bonding is thus shown to be a key factor for the binding of bacteriochlorophyll and assembly of this model cofactor-polypeptide site.     

Modular design of synthetic protein mimics. Characterization of the helical conformation of a 13-residue peptide in crystals

The incorporation of alpha-aminoisobutyryl (Aib) residues into peptide sequences facilitates helical folding. Aib-containing sequences have been chosen for the design of rigid helical segments in a modular approach to the construction of a synthetic protein mimic. The helical conformation of the synthetic peptide Boc-Aib-(Val-Ala-Leu-Aib)3-OMe in crystals is established by X-ray diffraction. The 13-residue apolar peptide adopts a helical form in the crystal with seven alpha-type hydrogen bonds in the middle and 3(10)-type hydrogen bonds at either end. The helices stack in columns, zigzag rather than linear, by means of direct NH...OC head to tail hydrogen bonds. Leucyl side chains are extended on one side of the helix and valyl side chains on the other side. Water molecules form hydrogen bonds with several backbone carbonyl oxygens that also participate in alpha-helix hydrogen bonds. There is no apparent distortion of the helix caused by hydration. The space group is P2(1)2(1)2(1), with a = 9.964 (3) A, b = 20.117 (3) A, c = 39.311 (6) A, Z = 4, and dx = 1.127 g/cm3 for C64H106N13O16.1.33H2O. The final agreement factor R was 0.089 for 3667 data observed greater than 3 sigma(F) with a resolution of 0.9 A.     

Conformational flexibility in a small globular hormone: X-ray analysis of avian pancreatic polypeptide at 0.98-Å resolution

The 36-amino acid avian pancreatic polypeptide has been studied by x-ray analysis at 0.98-Å resolution and refined using a restrained least-squares technique to an agreement factor of 15.6%. The polypeptide, which has a compact globular structure with a hydrophobic core, comprises a polyproline–like helix (residues 2–8) and an α-helix (residues 14–32). The molecule forms symmetrical dimers linked through zinc atoms in the crystal lattice. The high-resolution analysis defines sequence-dependent distortions in the α-helical parameters due to hydrogen bonding of water molecules and side chains. The thermal parameters indicate an increased flexibility of the main chain at the turn between the helices and in the C-terminal residues. For the first time, six-parameter anisotropic thermal ellipsoids have been refined for each atom; these define the directions of the molecular motions in the polypeptide, indicating concerted vibrations. The physiological roles of conformation, flexibility, and dynamics of this polypeptide hormone are discussed.     

Crystal and molecular structure of the doubly unsaturated dehydropeptide Ac-delta Phe-Ala-delta Phe-NH-Me.

The dehydropeptide Ac-delta Phe-L-Ala-delta Phe-NH-Me, containing two dehydro-phenylalanine (delta Phe) residues, crystallizes from methanol/water in space group P2(1)2(1)2(1), with a = 12.508 (2), b = 12.746 (1) and c = 15.465 (9). In the crystalline state, the peptide chain assumes a right-handed 3(10)-helical conformation stabilized by two intramolecular hydrogen bonds, between the N-terminal acetyl group and the NH of delta Phe3, and between the CO of delta Phe1 and the NH of the C-terminal methylamide group, respectively. The two consecutive 10-membered rings formed by the hydrogen bonds have torsion angles quite close to the standard values for type III beta-bends. delta Phe1 is located in the (i + 1) position of the first beta-bend, while delta Phe2 is located in the (i + 2) position of the other beta-bend. In the crystal, the molecules are linked head to tail by intermolecular hydrogen bonds to form long helical chains. The axes of the helices are parallel to the c axis, but neighboring helices run in antiparallel directions. This crystal packing is similar to the packing motifs frequently observed in Aib-containing peptides.