Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I 'beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I' beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 -> 1 hydrogen bonds. In addition, a single 4 -> 1 hydrogen bond is also observed at the N-terminus. All live Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C-alpha-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean r values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Hybrid peptide design. Hydrogen bonded conformations in peptides containing the stereochemically constrained gamma-amino acid residue, gabapentin

he crystal structure of 12 peptides containing the conformationally constrained 1-(aminomethyl)cyclohexaneacetic acid, gabapentin (Gpn), are reported. In all the 39 Gpn residues conformationally characterized so far, the torsion angles about the C-alpha-C-beta and C-beta-C-gamma bonds are restricted to the gauche conformation (+/- 60 degrees). The Gpn residue is constrained to adopt folded conformations resulting in the formation of intramolecularly hydrogen-bonded structures even in short peptides. The peptides Boc-Ac(6)c-Gpn-OMe 1 and Boc-Gpn-Aib-Gpn-Aib-OMe 2 provide examples of C-7 conformation; peptides Boc-Gpn-Aib-OH 3, Boc-Ac(6)c-Gpn-OH 4, Boc-Val-Pro-Gpn-OH 5, Piv-Pro-Gpn-Val-OMe 6, and Boc-Gpn-Gpn-Leu-OMe 7 provide examples of C-9 conformation; peptide Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8 provides an example of C-12 conformation and peptides Boc-beta Leu-Gpn-Val-OMe 9 and Boc-beta Phe-Gpn-Phe-OMe 10 provide examples of C-13 conformation. Gpn peptides provide examples of backbone expanded mimetics for canonical alpha-peptide turns like the gamma (C-7) and the beta (C-10) turns. The hybrid beta gamma sequences provide an example of a mimetic of the C-13 alpha-turn formed by three contiguous alpha-amino acid residues. Two examples of folded tripeptide structures, Boc-Gpn-beta Phe-Leu-OMe 11 and Boc-Aib-Gpn-beta Phg-NHMe 12, lacking internal hydrogen bonds are also presented. An analysis of available Gpn residue conformations provides the basis for future design of folded hybrid peptides.

Solution conformation of a tetradecapeptide stabilized by two di-n-propyl glycine residues

The solution conformation of a designed tetradecapeptide Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (Dpg-14) containing two di-n-propyl glycine (Dpg) residues has been investigated by H-1 NMR and circular dichroism in organic solvents. The peptide aggregates formed at a concentration of 3 mm in the apolar solvent CDCl3 were broken by the addition of 12% v/v of the more polar solvent DMSO-d(6). Successive NiH <-> Ni+1H NOEs observed over the entire length of the sequence in this solvent mixture together with the observation of several characteristic medium-range NOEs support a major population of continuous helical conformations for Dpg-14. Majority of the observed coupling constants ((3)(alpha)(JNHC)(H)) also support phi values in the helical conformation. Circular dichroism spectra recorded in methanol and propan-2-ol give further support in favor of helical conformation for Dpg-14 and the stability of the helix at higher temperature. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.

A glossary of DNA structures from A to Z

The right-handed double-helical Watson-Crick model for B-form DNA is the most commonly known DNA structure. In addition to this classic structure, several other forms of DNA have been observed and it is clear that the DNA molecule can assume different structures depending on the base sequence and environment. The various forms of DNA have been identified as A, B, C etc. In fact, a detailed inspection of the literature reveals that only the letters F, Q, U, V and Y are now available to describe any new DNA structure that may appear in the future. It is also apparent that it may be more relevant to talk about the A, B or C type dinucleotide steps, since several recent structures show mixtures of various different geometries and a careful analysis is essential before identifying it as a 'new structure'. This review provides a glossary of currently identified DNA structures and is quite timely as it outlines the present understanding of DNA structure exactly 50 years after the original discovery of DNA structure by Watson and Crick

Analysis of texture evolution in pure magnesium and the magnesium alloy AM30 during rod and tube extrusion

The evolution of microstructure and texture during extrusion of pure magnesium and its single phase alloy AM30 has been studied experimentally as well as by crystal plasticity simulation. Microstructure and micro-texture were characterized by electron back scattered diffraction (EBSD), bulk-texture was measured using X-ray diffraction and deformation texture simulations were carried out using visco-plastic self consistent (VPSC) model. In spite of clear indications of the occurrence of dynamic recrystallization (DRX), simulations were able to reproduce the experimental textures successfully. This was attributed to the fact that the textures were c-type fibers with their axis of rotation parallel to the c-axis and DRX leads to simply rotate the texture around the c-axis. (C) 2011 Elsevier B.V. All rights reserved.

Transplanting the n-terminus from Kv1.4 to Kv1.1 generates an inwardly rectifying K+ channel

A chimeric channel, 4N/1, was generated from two outwardly rectifying K+ channels by linking the N-terminal cytoplasmic domain of hKv1.4 (N terminus ball and chain of hKv1.4) with the transmembrane body of hKvl.l (Delta 78N1 construct of hKvl.l). The recombinant channel has properties similar to the six transmembrane inward rectifiers and opens on hyperpolarization with a threshold of activation at -90 mV. Outward currents are seen on depolarization provided the channel is first exposed to a hyperpolarizing pulse of -100mV or more. Hyperpolarization at and beyond -130mV provides evidence of channel deactivation. Delta 78N1 does not show inward currents on hyperpolarization but does open on depolarizing from -80mV with characteristics similar to native hKvl.l. The outward currents seen in both Delta 78N1 and 4N/1 inactivate slowly at rates consistent with C-type inactivation. The inward rectification of the 4N/1 chimera is consistent with the inactivation gating mechanism. This implies that the addition of the N-terminus from hKv1.4 to hKvl.l shifts channel activation to hyperpolarizing potentials. These results suggest a mechanism involving the N-terminal cytoplasmic domain for conversion of outward rectifiers to inward rectifiers. (C) 1999 Lippincott Williams & Wilkins.

High temperature phase chemistry of system Eu-Pd-O

An isothermal section of the phase diagram for the system Eu - Pd - O at 1223 K has been established by equilibration of samples representing 20 different compositions, and phase identification after quenching by optical and scanning electron microscopy, X-ray powder diffraction, and energy dispersive spectroscopy. Three ternary oxides, Eu4PdO7, Eu2PdO4, and Eu2Pd2O5, were identified. Liquid alloys and the intermetallic compounds EuPd2 and EuPd3 were found to be in equilibrium with EuO. The compound EuPd3 was also found to coexist separately with Eu3O4 and Eu2O3. The oxide phase in equilibrium with EuPd5 and Pd rich solid solution was Eu2O3. Based on the phase relations, four solid state cells were designed to measure the Gibbs energies of formation of the three ternary oxides in the temperature range from 925 to 1350 K. Although three cells are sufficient to obtain the properties of the three compounds, the fourth cell was deployed to crosscheck the data. An advanced version of the solid state cell incorporating a buffer electrode with yttria stabilised zirconia solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa as the reference electrode was used for high temperature thermodynamic measurements. Equations for the standard Gibbs energy of formation of the interoxide compounds from their component binary oxides Eu2O3 with C type structure and PdO have been established. Based on the thermodynamic information, isothermal chemical potential diagrams and isobaric phase diagrams for the system Eu - Pd - O have been developed.

Systematic trends in structural and thermodynamic properties of ternary oxides in the systems Ln-Pd-O (Ln = lanthanide element)

Isothermal sections of the phase diagrams for the systems Ln-Pd-O (Ln = lanthanide element) at 1223 K indicate the presence of two inter-oxide compounds Ln(4)PdO(7) and Ln(2)Pd(2)O(5) for Ln = La, Pr, Nd, Sm, three compounds Ln(4)PdO(7), Ln(2)PdO(4) and Ln(2)Pd(2)O(5) for Ln = Eu, Gd and only one compound of Ln(2)Pd(2)O(5) for Ln = Tb to Ho. The lattice parameters of the compounds Ln(4)PdO(7), Ln(2)PdO(4) and Ln(2)Pd(2)O(5) show systematic nonlinear variation with atomic number. The unit cell volumes decrease with increasing atomic number. The standard Gibbs energies, enthalpies and entropies of formation of the ternary oxides from their component binary oxides (Ln(2)O(3) and PdO) have been measured recently using an advanced version of the solid-state electrochemical cell. The Gibbs energies and enthalpies of formation become less negative with increasing atomic number of Ln. For all the three compounds, the variation in Gibbs energy and enthalpy of formation with atomic number is markedly non-linear. The decrease in stability with atomic number is most pronounced for Ln(2)Pd(2)O(5), followed by Ln(4)PdO(7) and Ln(2)PdO(4). This is probably related to the repulsion between Pd2+ ions on the opposite phases Of O-8 cubes in Ln(2)Pd(2)O(5), and the presence of Ln-filled O-8 cubes that share three faces with each other in Ln4PdO7. The values for entropy of formation of all the ternary oxides from their component binary oxides are relatively small. Although the entropies of formation show some scatter, the average value for Ln = La, Pr, Nd is more negative than the average value for the other lanthanide elements. From this difference, an average value for the structure transformation entropy of Ln(2)O(3) from C-type to A-type is estimated as 0.87 J.mol(-1).K-1. The standard Gibbs energies of formation of these ternary oxides from elements at 1223 K are presented as a function of lanthanide atomic number. By invoking the Neumann-Kopp rule for heat capacity, thermodynamic properties of the inter-oxide compounds at 298.15 K are estimated. (C) 2002 Elsevier Science Ltd. All rights reserved.

Lepton masses and flavor violation in the Randall-Sundrum model

Lepton masses and mixing angles via localization of 5-dimensional fields in the bulk are revisited in the context of Randall-Sundrum models. The Higgs is assumed to be localized on the IR brane. Three cases for neutrino masses are considered: (a) The higher-dimensional neutrino mass operator (LH.LH), (b) Dirac masses, and (c) Type I seesaw with bulk Majorana mass terms. Neutrino masses and mixing as well as charged lepton masses are fit in the first two cases using chi(2) minimization for the bulk mass parameters, while varying the O(1) Yukawa couplings between 0.1 and 4. Lepton flavor violation is studied for all the three cases. It is shown that large negative bulk mass parameters are required for the right-handed fields to fit the data in the LH.LH case. This case is characterized by a very large Kaluza-Klein (KK) spectrum and relatively weak flavor-violating constraints at leading order. The zero modes for the charged singlets are composite in this case, and their corresponding effective 4-dimensional Yukawa couplings to the KK modes could be large. For the Dirac case, good fits can be obtained for the bulk mass parameters, c(i), lying between 0 and 1. However, most of the ``best-fit regions'' are ruled out from flavor-violating constraints. In the bulk Majorana terms case, we have solved the profile equations numerically. We give example points for inverted hierarchy and normal hierarchy of neutrino masses. Lepton flavor violating rates are large for these points. We then discuss various minimal flavor violation schemes for Dirac and bulk Majorana cases. In the Dirac case with minimal-flavor-violation hypothesis, it is possible to simultaneously fit leptonic masses and mixing angles and alleviate lepton flavor violating constraints for KK modes with masses of around 3 TeV. Similar examples are also provided in the Majorana case.

Identification of mycobacterial lectins from genomic data

Sixty-four sequences containing lectin domains with homologs of known three-dimensional structure were identified through a search of mycobacterial genomes. They appear to belong to the -prism II, the C-type, the Microcystis virdis (MV), and the -trefoil lectin folds. The first three always occur in conjunction with the LysM, the PI-PLC, and the -grasp domains, respectively while mycobacterial -trefoil lectins are unaccompanied by any other domain. Thirty heparin binding hemagglutinins (HBHA), already annotated, have also been included in the study although they have no homologs of known three-dimensional structure. The biological role of HBHA has been well characterized. A comparison between the sequences of the lectin from pathogenic and nonpathogenic mycobacteria provides insights into the carbohydrate binding region of the molecule, but the structure of the molecule is yet to be determined. A reasonable picture of the structural features of other mycobacterial proteins containing one or the other of the four lectin domains can be gleaned through the examination of homologs proteins, although the structure of none of them is available. Their biological role is also yet to be elucidated. The work presented here is among the first steps towards exploring the almost unexplored area of the structural biology of mycobacterial lectins. Proteins 2013. (c) 2012 Wiley Periodicals, Inc.

Microwave Spectroscopic and Atoms in Molecules Theoretical Investigations on the ArPropargyl Alcohol Complex: ArHO, Ar, and ArC Interactions

The structure of the Arpropargyl alcohol (ArPA) complex is determined from the rotational spectra of the parent complex and its two deuterated isotopologues, namely ArPA-D(OD) and ArPA-D(CD). The spectra confirm a geometry in which PA exists in the gauche form with Ar located in between OH and CCH groups. All a, b and c types of transitions show small splitting due to some large-amplitude motion dominated by COH torsion, as in the monomer. Splittings in a- and b-type transitions are of the order of a few kilohertz, whereas splitting in the c-type transitions is relatively larger (0.92.6 MHz) and decreases in the order ArPA>ArPA-D(CD)>ArPA-D(OD). The assignments are well supported by ab initio calculations. Atoms in molecules (AIM) and electrostatic potential calculations are used to explore the nature of the interactions in this complex. AIM calculations not only reveal the expected OHAr and Ar interactions in the Argauche-PA complex, but also novel CAr (of CH2OH group) and OHAr interactions in the Artrans-PA complex. Similar interactions are also present in the Armethanol complex.

Corticosterone Treatment Results in Enhanced Release of Peptidergic Vesicles in Astrocytes via Cytoskeletal Rearrangements

While the effect of stress on neuronal physiology is widely studied, its effect on the functionality of astrocytes is not well understood. We studied the effect of high doses of stress hormone corticosterone, on two physiological properties of astrocytes, i.e., gliotransmission and interastrocytic calcium waves. To study the release of peptidergic vesicles from astrocytes, hippocampal astrocyte cultures were transfected with a plasmid to express pro-atrial natriuretic peptide (ANP) fused with the emerald green fluorescent protein (ANP.emd). The rate of decrease in fluorescence of ANP.emd on application of ionomycin, a calcium ionophore was monitored. Significant increase in the rate of calcium-dependent exocytosis of ANP.emd was observed with the 100 nM and 1 M corticosterone treatments for 3 h, which depended on the activation of the glucocorticoid receptor. ANP.emd tagged vesicles exhibited increased mobility in astrocyte culture upon corticosterone treatment. Increasing corticosterone concentrations also resulted in concomitant increase in the calcium wave propagation velocity, initiated by focal ATP application. Corticosterone treatment also resulted in increased GFAP expression and F-actin rearrangements. FITC-Phalloidin immunostaining revealed increased formation of cross linked F-actin networks with the 100 nM and 1 M corticosterone treatment. Alternatively, blockade of actin polymerization and disruption of microtubules prevented the corticosterone-mediated increase in ANP.emd release kinetics. This study reports for the first time the effect of corticosterone on gliotransmission via modulation of cytoskeletal elements. As ANP acts on both neurons and blood vessels, modulation of its release could have functional implications in neurovascular coupling under pathophysiological conditions of stress.

Phase equilibria in the system Sm-Rh-O and thermodynamic and thermal studies on SmRhO3

Using isothermal equilibration, phase relations are established in the system Sm-Rh-O at 1273 K. SmRhO3 with GdFeO3-type perovskite structure is found to be the only ternary phase. Solid-state electrochemical cells, containing calcia-stabilized zirconia as an electrolyte, are used to measure the thermodynamic properties of SmRhO3 formed from their binary component oxides Rh2O3 (ortho) and Sm2O3 (C-type and B-type) in two different temperature ranges. Results suggest that C-type Sm2O3 with cubic structure transforms to B-type Sm2O3 with monoclinic structure at 1110 K. The standard Gibbs energy of transformation is . Standard Gibbs energy of formation of SmRhO3 from binary component oxides Rh2O3 and Sm2O3 with B-type rare earth oxide structure can be expressed as . The decomposition temperature of SmRhO3 estimated from the extrapolation of electrochemical data is 1665 (+/- 2) K in air and 1773 (+/- 3) K in pure oxygen. Temperature-composition diagrams at constant oxygen pressures are constructed for the system Sm-Rh-O. Employing the thermodynamic data for SmRhO3 from emf measurement and auxiliary data for other phases from the literature, oxygen potential-composition phase diagram and 3-D chemical potential diagram for the system Sm-Rh-O at 1273 K are developed.

Novel M-Superfamily and T-Superfamily conotoxins and contryphans from the vermivorous snail Conus figulinus

The venom of Conus figulinus, a vermivorous cone snail, found in the south east coast of India, has been studied in an effort to identify novel peptide toxins. The amino acid sequences of seven peptides have been established using de novo mass spectrometric based sequencing methods. Among these, three peptides belong to the M-Superfamily conotoxins, namely, Fi3a, Fi3b, and Fi3c, and one that belongs to the T-Superfamily, namely, Fi5a. The other three peptides are contryphans, namely, contryphans fib, fic, and fid. Of these Fi3b, Fi3c, Fi5a, and contryphan fib are novel and are reported for the first time from venom of C.figulinus. The details of the sequencing methods and the relationship of these peptides with other M'-Superfamily conotoxins from the fish hunting and mollusk hunting clades are discussed. These novel peptides could serve as a lead compounds for the development of neuropharmacologically important drugs. Copyright (c) 2014 European Peptide Society and John Wiley & Sons, Ltd.

A delocalizable cationic headgroup together with an oligo-oxyethylene spacer in gemini cationic lipids improves their biological activity as vectors of plasmid DNA

Lipoplex nano-aggregates constituted of plasmid DNA (pDNA) pEGFP-C3 and mixed cationic liposomes, consisting of several percentages of a gemini cationic lipid (GCL) of the 1,2-bis(hexadecyl imidazolium) oxyethylene series, referred to as (C(16)Im)(2)(C2O)(n), with oxyethylene spacers (n = 1, 2 or 3) between the imidazolium cationic groups and the DOPE zwitterionic helper lipid, have been characterized by various biophysical and biological approaches carried out at several GCL compositions (alpha), and either the mass or the effective charge ratio of the lipoplex. The electrochemical study by zeta-potential confirms that the three GCLs yield a 10% lower effective charge than the nominal one, while compacted pDNA yields only a 25% effective negative charge. The SAXS study reveals, irrespective of the spacer length (n) and effective charge ratio (rho(eff)), the presence of two lamellar structures, i.e., one (L-alpha,L-main) in the whole GCL composition and another (L-alpha,L-DOPE,L-rich) with higher periodicity values that coexists with the previous one at low GCL composition (alpha = 0.2). The cryo-TEM analysis shows two types of multilamellar structures consisting of cationic lipidic bilayers with pDNA sandwiched between them: a cluster-type (C-type) at low alpha = 0.2 and a fingerprint-type (FP-type) at alpha >= 0.5, both with similar interlamellar spacing (d) in agreement with the L-alpha,L-main structure determined by SAXS. Transfection efficacies (TEs) of each lipid mixture were determined in four different cell lines (HEK293T, HeLa, Caco-2 and A549) at several alpha and rho(eff) values in the absence and presence of serum (FBS). The optimized formulations (alpha = 0.2 and rho(eff) = 2.0) substantially transfect cells much better than a commercial transfection reagent, Lipofectamine 2000 and previously studied efficient lipoplexes containing other cationic head groups or spacers both in the absence and presence of serum. The activity of optimized formulations may be attributed to the combination of several factors, such as: (a) the fusogenic character of DOPE which results in higher fluidity of the lipoplexes at alpha = 0.2, (b) the coexistence of two lamellar structures at alpha = 0.2 that synergizes the TE of these lipid vectors, and mainly (c) the higher biocompatibility of the GCLs reported in this work due to the presence of two imidazolium cationic groups together with an oligo-oxyethylene spacer. The length of the spacer in the GCL seems to have less impact, although (C(16)Im)(2)(C2O)(n)/DOPEpDNA lipoplexes with n = 1 and 3 show higher gene transfection than n = 2. All the optimum formulations reported herein are all highly efficient with negligible levels of toxicity, and thus, may be considered as very promising gene vectors for in vivo applications.