The stereochemistry of a-aminoisobutyric acid containing peptides

a-Aminoisobutyric acid (Aib), * a nonprotein amino acid first described synthetically, I has been found in diverse sources, ranging from peptides of microbial origin2s3 to the Murchison mete~r i te.E~a rly studies of the chemistry of Aib were directed towards the synthesis of model peptides containing this "sterically hindered" amino There have been several reports on the synthesis of Aib containing analogs of biologically active peptides.

Electrophilic Substitution Reactions of Copper(II) Acetylacetoneimine Complexes with Arene Diazonium Ions

Copper(II) complexes of ethylene/propylene-bis(acetylacetoneimine), Cu(baen) or Cu(bapn), react quickly and quantitatively in aqueous methanol at the methine position with arene diazonium ions in a stepwise manner to yield mono- and di-substituted copper(II) complexes. All the complexes are paramagnetic with μeff∼1.88 B.M. In all the complexes the diazo substituted part of the ligand coordinates to the metal through the agr-nitrogen of the azo group and the imine nitrogen, forming glyoxaliminearylhydrazone type of ligand system. The complexes have been characterized by elemental analysis, electronic, esr, ir and mass spectroscopic methods.

A helical peptide containing a majority of valyl residues. The crystal structure of t-butyloxy- carbonyl-(L-valyl-_-aminoisobutyryl)3-L-valyl methyl ester onohydrate

The monohydrate of the heptapeptide t-butyloxycarbonyl-(L-valyl-α-aminoiso-butyryl)3-L-valyl methyl ester crystallizes in the orthorhombic space group P212121 with four molecules in a unit cell with the dimensions α= 9.375, b = 19.413 and c = 25.878 ÅA. The structure has been solved by direct methods and refined to an R value of 0.059 for 3633 observed reflections. The molecule in the structure exists as a slightly distorted 310-helix stabilized by five 4 -> 1 intramolecular hydrogen bonds, indicating the overwhelming influence of α-aminoisobutyryl (Aib) residues in dictating helical fold even when a majority of residues in the peptide have a low intrinsic propensity to be in helices. Contrary to what is expected in helical structures, the valyl side chains, two of which are disordered, exhibit all three possible conformations. The molecules arrange themselves in a head-to-tail fashion along the c-axis. The columns thus generated pack nearly hexagonally in the crystal.

Stereochemistry of peptides containing 1-aminocyclopentane carboxylic acid (Acc5). Solution and solid state conformations of Boc-Acc5-Acc5-NHMe.

The conformational analysis of a protected homodipeptide of 1-aminocyclopentanecarboxylic acid (Acc5) has been carried out. 1H-nmr studies establish a ?-turn conformation for Boc-Acc5-Acc5-NHMe in chloroform and dimethylsulfoxide solutions involving the methylamide NH in an intramolecular hydrogen bond. Supportive evidence for the formation of an intramolecular hydrogen bond is obtained from ir studies. X-ray diffraction studies reveal a type III ?-turn conformation in the solid state stabilized by a 4 ? 1 hydrogen bond between the Boc CO and methylamide NH groups. The ?,? values for both Acc5 residues are close to those expected for an ideal 310-helical conformation (?? ± 60°, ?? ±30°).

Stereochemically constrained peptides. Theoretical and experimental studies on the conformations of peptides containing 1-aminocyclohexane carboxylic acid

Conformational energy calculations on the model system N-acetyl- 1 -aminocyclohexanecarboxylic acid N'methylamide (Ac-Acc6-NHMe), using an average geometry derived from 13 crystallographic observations, establish that the Acc6 residue is constrained to adopt conformations in the helical regions of In contrast, the a,a-dialkylated residue with linear hydrocarbon side chains, a,a-di-n-propylglycine favors fully extended backbone structures (6 1= $ = 180'). The crystal structures of two model peptides, Boc-(Acc6),-OMe (type 111 @-turn at -Acc6(1)-Acc6(2)-) and Boc-Pro-Acc6-Ala-OMe (type I1 P-turn at -Pro-Acc6-), establish that Acc6 residues can occupy either position of type 111 P-turns and the i + 2 position of type I1 @-turns. The stereochemical rigidity of these peptides is demonstrated in solution by NMR studies, which establish the presence of one intramolecular hydrogen bond in each peptide in CDCI, and (CDJ2S0. Nuclear Overhauser effects permit characterization of the @-turn conformations in solution and establish their similarity to the solid-state structures. The implications for the use of Acc6 residues in conformational design are considered.

Conformations of dehydrophenylalanine containing peptides. NMR studies on three tripeptides with a central dehydrophenylalanyl residue.

Three tripeptides containing a central Z-dehydrophenylalanine residue (Δz-Phe), Boc-L-Phe-Δz-Phe-X-OMe (X = L-Val 1, L-Leu 2 and X = L-Ala 3) have been synthesized and their solution conformations investigated by 270 MHz 1H NMR spectroscopy. In all three peptides, conformations involving the X residue NH in an intramolecular hydrogen bond were favoured in CDCl3 solutions. Studies of the nuclear Overhauser effect (NOE) provided support for a Type II β turn conformation in these peptides with Phe and Δz-Phe occupying the i + 1 and i + 2 positions, respectively. Significantly different conformations lacking any intramolecular hydrogen bonds were observed for peptide 1 in (CD3)2SO. NOE results were consistent with a significant population of molecules having semi-extended conformations (ø > 100°) at the Δz-Phe residue.

Conformation of a 16-residue zervamicin IIA analog peptide containing three different structural features: 310-helix, alpha helix and ß-bend ribbon

Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib- Pro-Ala-Aib-Pro-Aib-Pro-Phe-OM(we here Boc is t-butoxycarbonyla nd Aib is a-aminoisobutyriac cid), a synthetica polar analog of the membrane-activefu ngal peptide antibioticz ervamtycinII A, crystallizesi n spaceg roupP 1 withZ =1 and cell parameters a = 9.086 ?0.002 A, b = 10.410 ?+ 0.002 A, c = 28.188 ? 0.004 A, a = 86.13 ? 0.01?, 13 = 87.90 ? 0.01?, and y = 89.27 ? 0.01?;o veralla greementf actorR = 7.3% for 7180 data (Fo > 3cr) and 0.91-A resolution. The peptide backbone makes a continuous spiral that begins as a 310-helix at the N-terminus, changes to an a-helix for two turns, and ends in a spiral of three fl-bends in a ribbon. Each of the fl-bends contains a proline residue at one of the corners. The torsion angles 4i range from -51? to -91? (average value -64o), and the torsion angles ai range from -1? to -46? (average value -31?). There are 10 intramolecularN H...OCh ydrogenb onds in the helix and two directh ead-to-taihl ydrogenb ondsb etween successive molecules. Two H20 and two CH30H solvent molecules fill additional space with appropriate hydrogen bonding in the head-to-tail region, and two additional H20 molecules form hydrogen bonds with carbonyl oxygens near the curve in the helix at Pro-10. Since there is only one peptide molecule per cell in space group P1, the molecules repeat only by translation, and consequently the helices pack parallel to each other.

Conformations of dehydrophenylalanyl containing peptides. Nuclear Overhauser effect study of two acyclic

Two isomeric, acyclic tetrapeptides containing a Z-dehydrophenylalanine residue (Δz-Phe) at position 2 or 3, Boc-Leu-Ala-Δz-Phe-Leu-OMe (1) and Boc-Leu-Δz-Phe-Ala-Leu-OMe (2), have been synthesized and their solution conformations investigated by 270MHz 1H n.m.r. spectroscopy. In peptide 1 the Leu(4) NH group appears to be partially shielded from solvent, while in peptide 2 both Ala(3) and Leu(4) NH groups show limited solvent accessibility. Extensive difference nuclear Overhauser effect (n.O.e.) studies establish the occurrence of several diagnostic inter-residue n.O.e.s (CαjH ⇆ Ni+1H and NiH ⇆ Ni+1H) between backbone protons. The simultaneous observation of “mutually exclusive” n.O.e.s suggests the presence of multiple solution conformations for both peptides. In peptide 1 the n.O.e. data are consistent with a dynamic equilibrium between an -Ala-Δz-Phe- Type II β-turn structure and a second species with Δz-Phe adopting a partially extended conformation with Ψ values of ± 100° to ± 150°. In peptide 2 the results are compatible with an equilibrium between a highly folded consecutive β-turn structure for the -Leu-Δz-Phe-Ala- segment and an almost completely extended conformation.

A XANES study of the K-absorption edge of copper in some of its compounds and use of the same in the determination of bond length

XANES in the K-edge of copper in the systems CuO, Cu(OH)2, La2CuO4, Cu3AsO4 and CuOHF have been investigated and transitions have been assigned to the observed structures. The measurements have been used for calculating the first coordination bond distance in the above systems. It is observed that the values so determined agree fairly well with crystallographic values.

Effect of Strain Rate on Evolution of the Deformation Microstructure and Texture in Polycrystalline Copper and Nickel

The evolution of crystallographic texture in polycrystalline copper and nickel has been studied. The deformation texture evolution in these two materials over seven orders of magnitude of strain rate from 3 x 10(-4) to similar to 2.0 x 10(+3) s(-1) show little dependence on the stacking fault energy (SFE) and the amount of deformation. Higher strain rate deformation in nickel leads to weakerh < 101 > texture because of extensive microband formation and grain fragmentation. This behavior, in turn, causes less plastic spin and hence retards texture evolution. Copper maintains the stable end < 101 > component over large strain rates (from 3 x 10(-4) to 10(+2) s(-1)) because of its higher strain-hardening rate that resists formation of deformation heterogeneities. At higher strain rates of the order of 2 x 10(+3) s(-1), the adiabatic temperature rise assists in continuous dynamic recrystallization that leads to an increase in the volume fraction of the < 101 > component. Thus, strain-hardening behavior plays a significant role in the texture evolution of face-centered cubic materials. In addition, factors governing the onset of restoration mechanisms like purity and melting point govern texture evolution at high strain rates. SFE may play a secondary role by governing the propensity of cross slip that in turn helps in the activation of restoration processes.

Correlations between frequency of infra-red active vibrational modes and copper-oxygen distance in copper oxides. Application to superconductors

The infra-red spectra of a large number of ternary Cu(II) oxides with at least a quasi square-planar coordination of oxygen around the copper ions have been studied. The frequency of the bands with the highest frequency,v max, is found to correlate extremely well with the shortest Cu–O distance.v max increases at an impressive rate of sim20 cm–1 per 0.01 Å when the Cu–O distance becomes less than 1.97 Å, which is the Cu2+–O2– distance in square-planar CuO4 complexes as obtained from empirical ionic radii considerations. The marked sensitivity may be used as a ldquotitrationrdquo procedure not only to assign bands but also to obtain diagnostic information about local coordination in compounds derived, for example, from the YBa2Cu3O7–d structure such as LaCaBaCu3O7–d . The only example where this correlation fails is in the two-layer non-superconducting oxides derived from La2(Ca, Sr)Cu2O6. The significance of this result is discussed. The marked dependence of frequency on the bond-distance is qualitatively examined in terms of an increased electron-phonon coupling to account for the observed tendency of the superconducting transition temperature to go through a maximum as the average basal plane Cu–O distance is decreased.

Crystallographic identification of a ‘stepped-cubane’ structure for the Cu4O4 core in [Cu4L2(bipy)4(µ3-OH)2][ClO4]4(HL = 5-hydroxy-6-methylpyridine-,4-dimethanol, bipy = 2,2′-bipyridine)

The structure of [Cu4L2(bipy)4(µ3-OH)2][ClO4]4 containing a Vitamin B6 ligand, pyridoxine (5-hydroxy-6-methylpyridine-3,4-dimethanol, HL), and 2,2′-bipyridine (bipy) has been determined by single-crystal X-ray analysis. This is the first report on a copper(II) complex having a ‘stepped-cubane’ structure. The compound crystallizes in the triclinic space group P[1 with combining macron](Z= 1) with a= 11.015(3), b= 11.902(1), c= 13.142(2)Å, α= 105.07(1), β= 102.22(1) and γ= 99.12(1)°; R= 0.054). The co-ordination geometry around each copper is trigonally distorted square pyramidal. Two of the basal sites are occupied by bipyridyl nitrogens in a bidentate fashion. The remaining basal positions for Cu(1) are filled by a phenolic oxygen and a 4-hydroxymethyl oxygen of the L moiety, whereas for Cu(2) they are occupied by two µ3-OH oxygens. The axial sites are occupied by a µ3-OH oxygen and the 4-hydroxymethyl oxygen of the same pyridoxine for Cu(1) and Cu(2), respectively. Both the bridging nature of the 4-hydroxymethyl oxygen of the L moiety and the unsymmetrical bridging nature of the µ3-OH groups with axial–equatorial bridging are novel features. The structure is discussed in relation to stepped-cubane structures reported in the literature. A comparative study is also made with µ3-hydroxo-bridged copper(II) complexes. Both the plasticity effect of CuII and the stacking interactions between the various rings appear to be important in stabilizing this unusual structure.

Direct current electrical resistivity of zinc borate glasses containing transition metal oxides

The resistivities of zinc borate glasses containing Fe2O3, V2O5, and Fe2O3 + V2O5 have been measured as a function of composition and temperature. The values of resistivity and activation energy decrease as the transition metal oxide content is increased. The conductivities of the glasses containing Fe2O3 + V2O5 are more than the sum of those of the glasses containing only Fe2O3 or V2O5 (i.e. the activation energies are less than the sum of those in the glasses containing only Fe2O3 or V2O5). The results are discussed in terms of existing theories.