The crystal structure of Z‐(Aib)10‐OH at 0.65 Å resolution: three complete turns of 310‐helix

The synthetic peptide Z‐(Aib)₁₀‐OH was crystallized from hot methanol by slow evaporation. The crystal used for data collection reflected synchrotron radiation to sub‐atomic resolution, where the bonding electron density becomes visible between the non‐hydrogen atoms. Crystals belong to the centrosymmetric space group P . Both molecules in the asymmetric unit form regular 3₁₀‐helices. All residues in each molecule possess the same handedness, which is in contrast to all other crystal structure determined to date of longer Aib‐homopeptides. These other peptides are C‐terminal protected by OtBu or OMe. In these cases, because of the missing ability of the C‐terminal protection group to form a hydrogen bond to the residue i‐3, the sense of the helix is reversed in the last residue. Here, the C‐terminal OH‐groups form hydrogen bonds to the residues i‐3, in part mediated by water molecules. This makes Z‐(Aib)₁₀‐OH an Aib‐homopeptide with three complete 3₁₀‐helical turns in spite of the shorter length it has compared with Z‐(Aib)₁₁‐OtBu, the only homopeptide to date with three complete turns.     

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.     

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.     

Synthetic peptide helices in crystals: structure and antiparallel and skewed packing motifs for alpha-helices in two isomeric decapeptides

The isomeric decapeptides Boc-Aib-Ala-Leu-Ala-Aib-Aib-Leu-Ala-Leu-Aib-OMe (II) and Boc-Aib-Ala-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Aib-OMe (III), are predominantly alpha-helical with little effect on the conformation with interchange of Aib/Ala residues or Aib/Leu residues. The packing motif of helices in crystal II is antiparallel, whereas the helices pack in a skewed fashion in crystal III, with a 40 degrees angle between neighboring helix axes. Crystal III contains a water molecule in a hydrophobic hole that forms hydrogen bonds with two carbonyl oxygens that also participate in 5----1 type hydrogen bonds. Values for helical torsional angles phi and psi assume a much wider range than anticipated. Crystal II: C49H88N10O13, space group P2(1), with a = 16.625 (2) A, b = 9.811 (5) A, c = 18.412 (3) A, beta = 99.79 (1) degrees, Z = 2, R = 5.7% for 4338 data with magnitude of F0' greater than 3 sigma(F). Crystal III: C49H88N10O13 x 1/2H2O, space group P2(1) with a = 11.072 (2) A, b = 34.663 (5) A, c = 16.446 (3) A, beta = 107.85 (1) degrees, Z = 4, R = 8.3% for 6087 data with [F0[ greater than 3 sigma(F).     

Conformational characteristics of peptides and unanticipated results from crystal structure analyses

Preferred conformation and types of molecular folding are some of the topics that can be addressed by structure analysis using x-ray diffraction of single crystals. The conformations of small linear peptide molecules with 2-6 residues are affected by polarity of solvent, presence of water molecules, hydrogen bonding with neighboring molecules, and other packing forces. Larger peptides, both cyclic and linear, have many intramolecular hydrogen bonds, the effect of which outweighs any intermolecular attractions. Numerous polymorphs of decapeptides grown from a variety of solvents, with different cocrystallized solvents, show a constant conformation for each peptide. Large conformational changes occur, however, upon complexation with metal ions. A new form of free valinomycin grown from DMSO exhibits near three-fold symmetry with only three intramolecular hydrogen bonds. The peptide is in the form of a shallow bowl with a hydrophobic exterior. Near the bottom of the interior of the bowl are three carbonyl oxygens, spaced and directed so that they are in position to form three ligands to a K+, e.g., complexation can be completed by the three lobes containing the beta-bends closing over and encapsulating the K+ ion. In another example, free antamanide and the biologically inactive perhydro analogue, in which four phenyl groups become cyclic hexyl groups, have essentially the same folding of backbone and side chains. The conformation changes drastically upon complexation with Li+ or Na+. However, the metal ion complex of natural antamanide has a hydrophobic globlar form whereas the metal ion complex of the inactive perhydro analogue has a polar band around the middle. The structure results indicate that the antamanide molecule is in a complexed form during its biological activity. Single crystal x-ray diffraction structure analyses have identified the manner in which water molecules are essential to creating minipolar areas on apolar helices. Completely apolar peptides, such as membrane-active peptides, can acquire amphiphilic character by insertion of a water molecule into the helical backbone of Boc-Aib-Ala-Leu-Aib-Ala-Leu-Aib-Ala-Leu-Aib-OMe, for example. The C-terminal half assumes an alpha-helix conformation, whereas the N-terminal half is distorted by an insertion of a water molecule W(1) between N(Ala5) and O(Ala2), forming hydrogen bonds N(5)H...W(1) and W(1)...O(2). The distortion of the helix exposes C = O(Aib1) and C = O(Aib4) to the outside environment with the consequence of attracting additional water molecules. The leucyl side chains are on the other side of the molecule. Thus a helix with an apolar sequence can mimic an amphiphilic helix.     

Design, synthesis, and crystal structure of self-assembling norbornene (NBE)-supported two-helix bundles: a unique example of Janus helicity in the solid-state structure of NBE(Aib(5))(2)

Norbornene-supported bis-helical peptides with the general structure NBE(Aib(n) )(2) (NBE: 2,3-trans-norbornene dicarbonyl unit; Aib: alpha,alpha'-dimethyl glycine unit; n = 4,5) have been synthesized and examined for self-assembly preferences in the solid state. An x-ray study has revealed a phenomenon of Janus helicity in the solid state structure of NBE(Aib(5))(2). The lower homologue NBE(Aib(4))(2), however, shows an identical screw sense for both the helical arms. The difference in the handedness of left and right arms is reflected in the self-assembly patterns. Thus, while the NBE(Aib(4))(2) molecule self-assembles to form an infinite hydrogen-bonded superhelical ladder, the Janus molecule NBE(Aib(5))(2) crystallizes as individual units surrounded by water molecules. The structures of Z-Aib(4)-OMe and Z-Aib(5)-OMe are also presented to compare their conformations with the helical arms of the title compound and also to the already known structures of other X-Aib(n) -Y compounds. The helices in all the molecules are the 3(10)-type.     

Crystal structure of Boc-Ala-Aib-Ala-Aib-Aib-methyl ester,a pentapeptide fragment of the channel-forming ionophore suzukacillin

t-Buthyoxycarbonyl-L -alanyl-α-aminiosobutyryl-L -alanyl-α-aminoisobutyryl-α-aminoisobutyric acid methyl ester (t-Boc-L -Ala-Aib-L -Ala-Aib-Aib-OMe), C₂₄H₄₃N₅O₈, an end-protected pentapeptide with a sequence corresponding to the 6th through the 10th residues in suzukacillin, crystallizes in the orthorhombic space group P2₁2₁2₁ with a = 11.671, b = 14.534, c = 17.906 Å and z = 4. The molecule exists as a right-handed 3₁₀-helix with a pitch of 6.026 Å. The helix is stabilized by three 4 → 1 hydrogen bonds with the NH groups of Ala(3), Aib(4), and Aib(5) hydrogen bonding to the carbonyl oxygens of t-Boc, Ala(1), and Aib(2), respectively. The helical molecules arrange themselves in a head-to-tail fashion along the a direction in such a way that the NH groups of Ala(1) and Aib(2) hydrogen bond to the carbonyl oxygens of Aib(4) and Aib(5), respectively, of a translationally related molecule. The helical columns thus formed close-pack nearly hexagonally to form the crystal.     

Controls exerted by the Aib residue: helix formation and helix reversal

The helix forming properties of the achiral alpha-amino isobutyric residue (Aib) have been demonstrated by numerous crystal structure analyses of designed and naturally occurring peptides containing one or more Aib residues in the sequence. Experimental and computational results concerning the type of helix obtained, whether the 3(10)-helix with 4 --> 1 type hydrogen bonds or the alpha-helix with 5 --> 1 hydrogen bonds or mixtures of the two, have been published. This paper deals with residues that, if inserted into a sequence, could perturb the helix-forming propensity afforded by the presence of Aib residues. Examples of structures will be presented in which Pro, Hyp, Gly-Gly, d-Ala-Gly, and Lac have been centrally placed in the sequence. In addition to the formation of helices, detailed experimentally obtained conformation information is presented for the role of the Aib residue in reversing the sense of the helix (the Schellman motif) with the consequent formation of the 6 --> 1 type hydrogen bond or a solvated 6 --> 1 hydrogen bond. Data are presented for 13 molecules with helix reversals at the C-terminus or near the center of the sequence.     

Molecular and crystal structures of Aib-containing oligopeptides Boc-Leu4-Aib-Leu4-OBzl and Boc-(Leu4-Aib)2-OBzl.

Sample peptides Boc-Leu4-Aib-Leu4-OBzl and Boc-(Leu4-Aib)2-OBzl, were crystallized by the solvent-evaporation method. Both crystals are monoclinic, with space group of P2(1) and Z = 2. The cell parameters are a = 16.580 (7), b = 21.105 (7), c = 11.583 (4) A, and beta = 104.90 (3) degrees (Boc-Leu4-Aib-Leu4-OBzl), and a = 15.247 (9), b = 19.04 (1), c = 16.311 (9) A, and beta = 117.10 (1) degrees [Boc-(Leu4-Aib)2-OBzl]. Crystal structures were solved by the direct method and refined to R values of 0.096 (the former peptide) and 0.112 (the latter). Peptide backbones fold into a right-handed alpha-helix, except for the C-terminal Aib residue in Boc-(Leu4-Aib)2-OBzl. Both peptide molecules are stabilized by six (the former) or seven (the latter) intramolecular (5----1) hydrogen bonds, and arranged in the head-to-tail fashion, which makes an infinite column. In this column, one (the former) or two (the latter) intermolecular hydrogen bonds link the neighboring molecules. In the case of Boc-Leu4-Aib-Leu4-OBzl, the solvent molecule N,N-dimethylformamide was found in the difference Fourier map. There was a hydrogen bond between peptide and solvent molecule. Along the lateral direction, only hydrophobic contacts were observed between adjacent peptide molecules.     

Conformations of helical Aib peptides containing a pair of l‐amino acid and d‐amino acid

A pair of l ‐leucine (l ‐Leu) and d ‐leucine (d ‐Leu) was incorporated into α‐aminoisobutyric acid (Aib) peptide segments. The dominant conformations of four hexapeptides, Boc‐l ‐Leu‐Aib‐Aib‐Aib‐Aib‐l ‐Leu‐OMe (1a), Boc‐d ‐Leu‐Aib‐Aib‐Aib‐Aib‐l ‐Leu‐OMe (1b), Boc‐Aib‐Aib‐l ‐Leu‐l ‐Leu‐Aib‐Aib‐OMe (2a), and Boc‐Aib‐Aib‐d ‐Leu‐l ‐Leu‐Aib‐Aib‐OMe (2b), were investigated by IR, ¹H NMR, CD spectra, and X‐ray crystallographic analysis. All peptides 1a,b and 2a,b formed 3₁₀‐helical structures in solution. X‐ray crystallographic analysis revealed that right‐handed (P) 3₁₀‐helices were present in 1a and 1b and a mixture of right‐handed (P) and left‐handed (M) 3₁₀‐helices was present in 2b in their crystalline states. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe

In the crystal, the backbone of Boc-(Aib-Val-Ala-Leu)2-Aib-OMe adopts a helical form with four alpha-type hydrogen bonds in the middle, flanked by 3(10)-type hydrogen bonds at either end. The helical molecules stack in columns with head-to-tail hydrogen bonds, either directly between NH and CO, or bridged by solvent molecules. The packing of the helices is parallel, even in space group P2(1). Cell parameters are a = 9.837(2) A, b = 15.565(3) A, c = 20.087(5) A, beta = 96.42(2) degrees, dcalc = 1.091 g/cm3 for C46H83N9O12.1.5H2O.0.67CH3OH. There appears to be some hydration of the backbone in this apolar helix.     

Molecular and crystal structures of N-arylglycopyranosylamines formed by reaction between sulfanilamide and D-ribose, D-arabinose and D-mannose

The X-ray crystal structures of three monosaccharide derivatives prepared by the reaction of sulfanilamide with D-ribose, D-arabinose, and D-mannose have been determined. The derivatives are N-(p-sulfamoylphenyl)-alpha-D-ribopyranosylamine (1), N-(p-sulfamoylphenyl)-alpha-D-arabinopyranosylamine (2), and N-(p-sulfamoylphenyl)-beta-D-mannopyranosylamine monohydrate (3). The monosaccharide ring of 1 and 2 has the 1C4 conformation, stabilized in 1 by an intramolecular hydrogen bond from 0-2 to 0-4. Compound 3 has the 4C1 conformation at the monosaccharide ring and the gt conformation at the C-6-O-6 side chain. Occupancy of the water molecule in the crystal of 3 actually examined was 22%. The degree of interaction between sulfamoyl groups and monosaccharide moieties varies from structure to structure. The packing arrangement of 2 involves hydrogen bonding between sulfamoyl groups and monosaccharide hydroxyl groups, but interactions of this type are fewer in 1, and in 3 the hydrogen bonds are either strictly between monosaccharide hydroxyl groups or strictly between sulfamoyl groups. Pairs of hydrogen bonds (two-point contacts) link neighboring molecules in all three structures, between screw-axially related molecules in 1 and 2 and between translationally related molecules in 3. The contact in 3 defined by the O-3-H...O-5 and O-6-H...O-4 hydrogen bonds is found in several other N-aryl-beta-D-mannopyranosylamine crystal structures and is apparently an especially favorable mode of intermolecular interaction in these compounds.     

Regularly alternating L,D-peptides. II. The double-stranded right-handed antiparallel beta-helix in the structure of t-Boc-(L-Phe-D-Phe)4-OMe

The crystal structure of Boc-(L-Phe-D-Phe)4-OMe has been determined by x-ray diffraction analysis. The peptide crystallizes in the triclinic system, space group P1 with a = 15.290 A, b = 15.163 A, c = 19.789 A, alpha = 102.49 degrees, beta = 96.59 degrees, gamma = 74.22 degrees, and Z = 2. The structure has been solved by coupling of the molecular replacement technique and expansion by tangent formula refinement of the set of known phases. Several cycles of Fourier calculations and least-squares refinement led to the location of 194 atoms of the two independent octapeptide chains and few molecules of cocrystallized solvent (chloroform, water, and methanol). The isotropic refinement converged to R = 0.13 for the 3077 "observed" reflections. The two independent octapeptide molecule form a dimer in the solid state: the two chains are associated by interstrand hydrogen bonds (12 of the type N-H ... O = C) with the formation of a double-stranded antiparallel right-handed -- beta 5.6-helix. These double helices can be represented as a cylinder with a hydrophilic inner core represented by the peptide units and an hydrophobic exterior constituted by the aromatic moieties. The dimensions of the cylinder are equal to those observed for Boc-(L-Val-D-Val)4-OMe. In the solid state the dimers pack with each other in an hexagonal fashion with the formation of layers; between the layers, solvent molecules fill empty spaces.     

The crystal and molecular structure of the alpha-helical nonapeptide antibiotic leucinostatin A

The crystal and molecular structure of the nonapeptide antibiotic leucinostatin A, containing some uncommon amino acids and three Aib residues, has been determined by x-ray diffraction analysis. The molecule crystallizes in the orthorhombic space group P2(1)2(1)2(1), a = 10.924, b = 17.810, c = 40.50 A, C62H111N11O13, HCl.H2O, Z = 4. The peptide backbone folds in a regular right-handed alpha-helix conformation, with six intramolecular i----(i + 4) hydrogen bonds, forming C13 rings. The nonapeptide chain includes at the C end an unusual beta-Ala residue, which also adopts the helical structure of the other eight residues. In the crystal the helices are linked head to tail by electrostatic and hydrogen-bond interactions, forming continuous helical rods. The crystal packing is formed by adjacent parallel and antiparallel helical rods. Between adjacent parallel helical columns there are only van der Waals contacts, while between adjacent antiparallel helical columns hydrogen-bond interactions are formed.     

Crystal structure of the topoisomerase II poison 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide bound to the DNA hexanucleotide d(CGTACG)2.

The structure of the complex formed between d(CGTACG)(2) and the antitumor agent 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide has been solved to a resolution of 1.6 A using X-ray crystallography. The complex crystallized in space group P6(4) with unit cell dimensions a = b = 30.2 A and c = 39.7 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains a single strand of DNA, 1. 5 drug molecules, and 29 water molecules. The final structure has an overall R factor of 19.3%. A drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the major groove, and the protonated dimethylamino group partially occupies positions close to ( approximately 3.0 A) the N7 and O6 atoms of guanine G2. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Sugar rings adopt the C2'-endo conformation except for cytosine C1 which moves to C3'-endo, thereby preventing steric collision between its C2' methylene group and the intercalated acridine ring. The intercalation cavity is opened by rotations of the main chain torsion angles alpha and gamma at guanines G2 and G6. Intercalation perturbs helix winding throughout the hexanucleotide compared to B-DNA, steps 1 and 2 being unwound by 8 degrees and 12 degrees, respectively, whereas the central TpA step is overwound by 17 degrees. An additional drug molecule, lying with the 2-fold axis in the plane of the acridine ring, is located at the end of each DNA helix, linking it to the next duplex to form a continuously stacked structure. The protonated N,N-dimethylamino group of this "end-stacked" drug hydrogen bonds to the N7 atom of guanine G6. In both drug molecules, the 4-carboxamide group is internally hydrogen bonded to the protonated N-10 atom of the acridine ring. The structure of the intercalated complex enables a rationalization of the known structure-activity relationships for inhibition of topoisomerase II activity, cytotoxicity, and DNA-binding kinetics for 9-aminoacridine-4-carboxamides.     

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

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(Aibn)2 (Py=2,6-pyridine dicarbonyl unit; Aib=alpha, alpha'-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 (Aibn-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 3(10)-helical structure, the presence of a well-formed 3(10)-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. P2(1)2(1)2(1), a=9.170(1) A, b=16.215(2) A, c=20.091(3) A, R=4.80; 1c, Py(Aib3)2, C33H51N7O10H2O, sp. gr. P1, a=11.040(1) A, b=12.367(1) A, c=16.959(1) A, alpha =102.41 degrees, beta =97.29 degrees, gamma =110.83 degrees, R1=6.94; 1 da, Py(Aib4)2.et ac, C41H65N9O12.1.5H2O.C4H8O2, sp. gr. P1, a=16.064(4) A, b=16.156 A, c=21.655(5) A, alpha =90.14(1)degrees, beta=101.38(2) degrees, gamma=97.07(1)degrees, Z=4, R1=9.03; 1db, Py(Aib4)2.amylac, C41H65N9O12.H2O.C7H14O2, P2(1)/c, a=16.890(1) A, b=17.523(1)A, c=20.411(1) A, beta=98.18 degrees, Z=4, R=11.1 (with disorder).     

Stereochemistry of Schellman motifs in peptides: Crystal structure of a hexapeptide with a C‐terminus 6 → 1 hydrogen bond

The Schellman motif is a widely observed helix terminating structural motif in proteins, which is generated when the C‐terminus residue adopts a left‐handed helical (α_L) conformation. The resulting hydrogen‐bonding pattern involves the formation of an intramolecular 6 → 1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the sequence. Thus far, the Schellman motif has been characterized crystallographically only in peptide helices of length 7 residues or greater. The structure of the hexapeptide Boc–Pro–Aib–Gly–Leu–Aib–Leu–OMe in crystals reveal a short helical stretch terminated by a Schellman motif, with the formation of 6 → 1 C‐terminus hydrogen bond. The crystals are in the space group P2₁2₁2₁ with a = 18.155(3) Å, b = 18.864(8) Å, c = 11.834(4) Å, and Z = 4 . The final R₁ and wR₂ values are 7.68 and 14.6%, respectively , for 1524 observed reflections [F_o ≥ 3ς(F_o)]. A 6 → 1 hydrogen bond between Pro(1)CO · · · Leu(6)NH and a 5 → 2 hydrogen bond between Aib(2)CO · · · Aib(5)NH are observed. An analysis of the available oligopeptides having an achiral Aib residue at the penultimate position suggests that chain length and sequence effects may be the other determining factors in formation of Schellman motifs. © 1999 John Wiley & Sons, Inc. Biopoly 50: 13–22, 1999     

Three complete turns of a 3(10)-helix at atomic resolution: the crystal structure of Z-(Aib)11-OtBu.

The crystal structure of the synthetic protected oligopeptide Z-(Aib)11-OtBu was determined by x-ray crystallography. The undecapeptide folds in a regular 3(10)-helix with nine consecutive 4 --> 1 hydrogen bonds. At present, this is the largest available structure of a homopeptide (including homopeptides consisting of standard amino acids) and also the longest observed regular 3(10)-helix at atomic resolution. Z-(Aib)11-OtBu crystallizes readily from hot ethanol-water mixture and is one of the crystals in which no solvent molecule is co-crystallized. In the crystal head-to-tail hydrogen bonded columns are formed in the [1 0 1] direction. Each helical column is surrounded by six others, whereby two are packed in parallel and four in antiparallel fashion. Helical columns are packed via apolar crystal contacts. The crystal structure of Z-(Aib)11-OtBu is compared with the crystal structures of Z-(Aib)10-OtBu and Z-(Aib)9-OtBu. The similarities and differences are analysed.     

Crystallographic characterization of the α,γ C12 helix in hybrid peptide sequences

The solid‐state conformations of two αγ hybrid peptides Boc‐[Aib‐γ⁴(R)Ile]₄‐OMe 1 and Boc‐[Aib‐γ⁴(R)Ile]₅‐OMe 2 are described. Peptides 1 and 2 adopt C₁₂‐helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C₁₂ motifs. The structure of peptide 2 reveals the formation of eight successive C₁₂ hydrogen‐bonded turns. Average backbone dihedral angles for αγ C₁₂ helices are peptide 1 , Aib; φ (°) = ?57.2 ± 0.8, ψ (°) = ?44.5 ± 4.7; γ⁴(R)Ile; φ (°) = ?127.3 ± 7.3, θ₁ (°) = 58.5 ± 12.1, θ₂ (°) = 67.6 ± 10.1, ψ (°) = ?126.2 ± 16.1; peptide 2 , Aib; φ (°) = ?58.8 ± 5.1, ψ (°) = ?40.3 ± 5.5; ψ⁴(R)Ile; φ (°) = ?123.9 ± 2.7, θ₁ (°) = 53.3 θ 4.9, θ ₂ (°) = 61.2 ± 1.6, ψ (°) = ?121.8 ± 5.1. The tendency of γ⁴‐substituted residues to adopt gauche–gauche conformations about the C^α–C^β and C^β–C^γ bonds facilitates helical folding. The αγ C₁₂ helix is a backbone expanded analog of α peptide 3₁₀ helix. The hydrogen bond parameters for α peptide 3₁₀ and α‐helices are compared with those for αγ hybrid C₁₂ helix. Copyright © 2016 European Peptide Society and John Wiley & Sons.     

Variability in the backbone conformation of cyclic pentapeptides. Crystal structure of cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala)

All the peptide bonds in cyclic(Gly-L-Pro-D-Phe-Gly-L-Ala) are in the trans conformation; however, the peptide bond C'5-N1 is twisted by 19 degrees from planarity (omega 5 = -161 degrees). A Type II beta-turn encompasses the L-Pro-D-Phe residues. Carbonyl oxygens O2, O4 and O5 are directed to the same side of the average plane through the backbone ring and they form hydrogen bonds with N3, N5 and N1, respectively, in adjacent molecules in a stacked column where the adjacent molecules are related by one translational unit. The conformation of the backbone is different from that established in other molecules with the DLDDL chirality sequence. The P21 cell contains two molecules of C21H26N5O5 with a = 4.836(2) A, b = 18.346(8) A, c = 12.464(5) A and beta = 100.05(4) degrees. The R factor for 1382 data with [F0[ greater than 1 sigma is 7.0%.