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Helical Structure (helical + structure)
Selected AbstractsNoncovalent Interactions in the Asymmetric Synthesis of Rigid, Conjugated Helical Structures,ANGEWANDTE CHEMIE, Issue 32 2009Makoto Miyasaka Dr. Von helicaler Faltung zu helicaler Fixierung: Das Tetrakis(,-trithiophen) 1 faltet sich in eine helicale Konformation (RRR), die eine doppelte Ringanellierung erleichtert und mit hoher Diastereoselektivität und mäßiger Enantioselektivität das Bis[7]helicen 2 (MRM) liefert. Diese starre, helical fixierte Struktur zeigt verbesserte chiroptische Eigenschaften, ähnlich denen des entsprechenden [15]Helicens. [source] A Dinuclear Double-Stranded Oxido Complex of ReV with a Bis(benzene- o -dithiolato) LigandEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 27 2009Jorge S. Gancheff Abstract The reaction of [ReOCl3(PPh3)2] with 1,2-bis(2,3-dimercaptobenzamido)ethane (H4 - 1) in the presence of Na2CO3 in methanol under anaerobic conditions affords the dinuclear ReV oxido complex [PPh4]2[ReO(1)]2 containing two distorted square-pyramidal {ReVOS4} units bridged by the ligand strands in a double-stranded fashion. The coordinationgeometry around the metal centers is similar to the one observed for [ReO(bdt)2],. The ReS4 planes are arranged in a coplanar fashion and are not twisted around the metal,metal vector, which prevents the complex to adopt a helical structure. Luminescence studies show the presence of emission bands, which are assigned to singlet-singlet transitions exhibiting very fast decays (ca. 10 ns). Theoretical Density Functional (DFT) studies on geometry and electronic properties were performed employing the hybrid B3LYP and PBE1PBE functionals. While the general trends observed in the experimental data are well reproduced in all cases, a good agreement was obtained using PBE1PBE, in particular for the Re,S bonds. Natural Bond Orbitals (NBO) analysis indicates the presence of polarized Re,O and Re,S bonds, both of them polarized toward the non-metal. The calculation show that the molecular orbitals of the ReV are doubly degenerated, the occupied 5d orbital of rhenium lying beneath occupied sulfur-based MOs due to the rigid geometry imposed by the C,C backbone of the bis(benzene- o -dithiolato) ligands. The origin of all absorption bands is ascribed to a ligand-to-metal charge transfer (LMCT), in which occupied sulfur-based orbitals and unoccupied rhenium-centered orbitals are involved.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Polymers or Supramolecules Generated From a New V-Shaped Bis-monodentate Ligand and the Effect of Steric Hindrance on Coordination Modes of the LigandEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 12 2006Caihua Zhou Abstract A new V-shaped bis-monodentate ligand L (L = 2,3,-dipyridylamine) (1) has been designed and synthesized by alkylation reaction of pyridylamine. An investigation of the charge distributions of the coordination atoms and single-point energy calculations of four conformers of ligand L based on the geometry of conformers optimized by the DFT (density functional theory) method was carried out. The results show that the four conformers of ligand L take on two stable and two less stable configurations. Theory forecasts that two relatively stable configurations present in complexes as probable coordination motifs of the ligand, and that steric hindrance of pyridine nitrogen atoms in isomers will affect its coordination ability together with the electronic factor. This forecast has been demonstrated by the coordination chemistry of ligand L, that is, configuration (a) and (b) of the ligand occur in the following reported complexes, which combines with AgI or CuII through two coordination modes (bidentate bridging or a monodentate mode) resulting in coordination polymers {[Ag (L)2]NO3}n (2), [Cu2(L)2(maa)4]n (maa = methacrylic acid) (3), and the mononuclear molecule [Cu(L)4](ClO4)2·2CH3CH2OH (4). The ligand assumes different coordination modes in the three complexes because of different levels of steric hindrance of the pyridine nitrogen atoms in the conformers. Interestingly, polymers 2 and 3 assume a 1D helical structure and a linear framework, respectively, and 4 has a 2D supramolecular architecture induced from hydrogen bond interactions. In addition, the magnetic properties of 3 have been explored, which shows a strong antiferromagnetic interaction.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Comparison of the aggregation properties, secondary structure and apoptotic effects of wild-type, Flemish and Dutch N-terminally truncated amyloid , peptidesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001N. Demeester Abstract The Dutch (E22Q) and Flemish (A21G) mutations in the ,APP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia. However, patients with these mutations express substantially different clinical phenotypes. Therefore, secondary structure and cytotoxic effects of the three A,(12,42) variants [wild-type (WT), Dutch and Flemish] were tested. At a concentration of 5 µm the aggregation of these peptides followed the order: A,(1,42) WT > A,(12,42) WT > A,(12,42) Flemish >,A,(12,42) Dutch. The stability of the secondary structure of these peptides upon decreasing the trifluoroethanol (TFE) concentration in the buffer was followed by circular dichroism measurements. WT peptides progressively lost their ,-helical structure; this change occurred faster for both the Flemish and Dutch peptides, and at higher percentages of TFE in the buffer, and was accompanied by an increase in ,-sheet and random coil content. Apoptosis was induced in neuronal cells by the A,(12,42) WT and Flemish peptides at concentrations as low as 1,5 µm, as evidenced by propidium iodide (PI) staining, DNA laddering and caspase-3 activity measurements. Even when longer incubation times and higher peptide concentrations were applied the N-truncated Dutch peptide did not induce apoptosis. Apoptosis induced by the full length A,(1,42) peptide was weaker than that induced by its N-truncated variant. These data suggest that N-truncation enhanced the cytotoxic effects of A, WT and Flemish peptides, which may play a role in the accelerated progression of dementia. [source] CuI -Catalyzed Azide,Alkyne Intramolecular i -to-(i+4) Side-Chain-to-Side-Chain Cyclization Promotes the Formation of Helix-Like Secondary StructuresEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2010Mario Scrima Abstract A solid-phase assembly of model peptides derived from human parathyroid hormone-related protein (11,19) containing ,-azido- and ,-yl-,-amino acid residues in positions i and i+4 was cyclised in solution by an intramolecular CuI -catalyzed azide,alkyne 1,3-dipolar Huisgen cycloaddition. These series of heterodetic cyclo-nonapeptides varied in the size of the disubstituted 1,2,3-triazolyl-containing bridge, the location and the orientation of the 1,2,3-triazolyl moiety within the bridge. The 1,2,3-triazolyl moiety, presented at either 1,4- or 4,1-orientation, is flanked by side chains containing 1,4 CH2 groups that result in bridges comprised from 4,7 CH2 groups connecting residues 13 and 17. Comprehensive conformational analysis employing CD, NMR and molecular dynamics reveals the conformational propensities of these heterodetic cyclo-nonapeptides. Cyclo-nonapeptides containing either the 7 methylene bridge (VII and VIII) or the 4 methylene bridge (II) are unstructured in structure-promoting solvent. Cyclo-nonapeptide I in which the 1,4-disubstituted 1,2,3-triazolyl is flanked by 3 and 1 CH2 groups in proximity to the respective residues 13 and 17, is stabilized in a non-canonical structure. All the other heterodetic cyclo-nonapeptides (III,VI) in which the 1,2,3-triazolyl is flanked by a total of 5 or 6 CH2 groups nicely accommodate ,-helical structures and reproduce very closely the helical structure stabilized by the analogous cyclo-nonapeptide in which Lys13 and Asp17 are bridged by the isosteric lactam. These studies suggest that the bioorthogonal i -to-(i+4) side-chain-to-side-chain cyclization via the prototypic "click reaction" offers a new and powerful approach for generating stable helix mimetic structures. [source] Elements of the C-terminal t peptide of acetylcholinesterase that determine amphiphilicity, homomeric and heteromeric associations, secretion and degradationFEBS JOURNAL, Issue 8 2004Stéphanie Belbeoc'h The C-terminal t peptide (40 residues) of vertebrate acetylcholinesterase (AChE) T subunits possesses a series of seven conserved aromatic residues and forms an amphiphilic ,-helix; it allows the formation of homo-oligomers (monomers, dimers and tetramers) and heteromeric associations with the anchoring proteins, ColQ and PRiMA, which contain a proline-rich motif (PRAD). We analyzed the influence of mutations in the t peptide of Torpedo AChET on oligomerization and secretion. Charged residues influenced the distribution of homo-oligomers but had little effect on the heteromeric association with QN, a PRAD-containing N-terminal fragment of ColQ. The formation of homo-tetramers and QN -linked tetramers required a central core of four aromatic residues and a peptide segment extending to residue 31; the last nine residues (32,40) were not necessary, although the formation of disulfide bonds by cysteine C37 stabilized T4 and T4,QN tetramers. The last two residues of the t peptide (EL) induced a partial intracellular retention; replacement of the C-terminal CAEL tetrapeptide by KDEL did not prevent tetramerization and heteromeric association with QN, indicating that these associations take place in the endoplasmic reticulum. Mutations that disorganize the ,-helical structure of the t peptide were found to enhance degradation. Co-expression with QN generally increased secretion, mostly as T4,QN complexes, but reduced it for some mutants. Thus, mutations in this small, autonomous interaction domain bring information on the features that determine oligomeric associations of AChET subunits and the choice between secretion and degradation. [source] Biophysical characterization of the interaction of high-density lipoprotein (HDL) with endotoxinsFEBS JOURNAL, Issue 23 2002Klaus Brandenburg The interaction of bacterial endotoxins [lipopolysaccharide (LPS) and the ,endotoxic principle' lipid A], with high-density lipoprotein (HDL) from serum was investigated with a variety of physical techniques and biological assays. HDL exhibited an increase in the gel to liquid crystalline phase transition temperature Tc and a rigidification of the acyl chains of the endotoxins as measured by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The functional groups of the endotoxins interacting with HDL are the phosphates and the diglucosamine backbone. The finding of phosphates as target groups is in accordance to measurements of the electrophoretic mobility showing that the zeta potential decreases from ,50 to ,60 mV to ,20 mV at binding saturation. The importance of the sugar backbone as further target structure is in accordance with the remaining negative potential and competition experiments with polymyxin B (PMB) and phase transition data of the system PMB/dephosphorylated LPS. Furthermore, endotoxin binding to HDL influences the secondary structure of the latter manifesting in a change from a mixed ,-helical/,-sheet structure to a predominantly ,-helical structure. The aggregate structure of the lipid A moiety of the endotoxins as determined by small-angle X-ray scattering shows a change of a unilamellar/inverted cubic into a multilamellar structure in the presence of HDL. Fluorescence resonance energy transfer data indicate an intercalation of pure HDL, and of [LPS],[HDL] complexes into phospholipid liposomes. Furthermore, HDL may enhance the lipopolysaccharide-binding protein-induced intercalation of LPS into phospholipid liposomes. Parallel to these observations, the LPS-induced cytokine production of human mononuclear cells and the reactivity in the Limulus test are strongly reduced by the addition of HDL. These data allow to develop a model of the [endotoxin]/[HDL] interaction. [source] Domain V of m-calpain shows the potential to form an oblique-orientated ,-helix, which may modulate the enzyme's activity via interactions with anionic lipidFEBS JOURNAL, Issue 22 2002Klaus Brandenburg The activity of m-calpain, a heterodimeric, Ca2+ -dependent cysteine protease appears to be modulated by membrane interactions involving oblique-orientated ,-helix formation by a segment, GTAMRILGGVI, in the protein's smaller subunit. Here, graphical and hydrophobic moment-based analyses predicted that this segment may form an ,-helix with strong structural resemblance to the influenza virus peptide, HA2, a known oblique-orientated ,-helix former. Fourier transform infrared spectroscopy showed that a peptide homologue of the GTAMRILGGVI segment, VP1, adopted low levels of ,-helical structure (, 20%) in the presence of zwitterionic lipid and induced a minor decrease (3 °C) in the gel to liquid-crystalline phase transition temperature, TC, of the hydrocarbon chains of zwitterionic membranes, suggesting interaction with the lipid headgroup region. In contrast, VP1 adopted high levels of ,-helical structure (65%) in the presence of anionic lipid, induced a large increase (10 °C) in the TC of anionic membranes, and showed high levels of anionic lipid monolayer penetration (,SP = 5.5 mN·m,1), suggesting deep levels of membrane penetration. VP1 showed strong haemolytic ability (LD50 = 1.45 mm), but in the presence of ionic agents, this ability, and that of VP1 to penetrate anionic lipid monolayers, was greatly reduced. In combination, our results suggest that m-calpain domain V may penetrate membranes via the adoption of an oblique-orientated ,-helix and electrostatic interactions. We speculate that these interactions may involve snorkelling by an arginine residue located in the polar face of this ,-helix. [source] NMR investigations of subunit c of the ATP synthase from Propionigenium modestum in chloroform/methanol/water (4 : 4 : 1)FEBS JOURNAL, Issue 7 2002Ulrich Matthey The subunit c from the ATP synthase of Propionigenium modestum was studied by NMR in chloroform/methanol/water (4 : 4 : 1). In this solvent, subunit c consists of two helical segments, comprised of residues L5 to I26 and G29 to N82, respectively. On comparing the secondary structure of subunit c from P. modestum in the organic solvent mixture with that in dodecylsulfate micelles several deviations became apparent: in the organic solvent, the interruption of the ,,helical structure within the conserved GXGXGXGX motif was shortened from five to two residues, the prominent interruption of the ,,helical structure in the cystoplasmic loop region was not apparent, and neither was there a break in the ,,helix after the sodium ion-binding Glu65 residue. The folding of subunit c of P. modestum in the organic solvent also deviated from that of Escherichia coli in the same environment, the most important difference being that subunit c of P. modestum did not adopt a stable hairpin structure like subunit c of E. coli. [source] The helix nucleation site and propensity of the synthetic mitochondrial presequence of ornithine carbamoyltransferaseFEBS JOURNAL, Issue 18 2000Harmen H. J. De Jongh This study describes the helix nucleation site and helix propagation of the amphiphilic helical structure of the mitochondrial presequence of rat ornithine carbamoyltransferase. We investigated this property of the 32-residue synthetic presequence using CD and 2D-HR NMR techniques by determining the structure as a function of the concentration of trifluoroethanol. It was found that the hydrophobic cluster Ile7-Leu8-Leu9 forms the helix nucleation site, expanding to include residues Asn4 to Lys16 when the concentration of trifluoroethanol is increased from 10 to 30%. At higher trifluoroethanol concentrations an increased ,stiffening' of the polypeptide backbone (to Arg26) is observed. In addition, by recording CD spectra at different trifluoroethanol concentrations as a function of temperature, it was found that the equilibrium constant between helix and random coil formation for this peptide exhibits a strong temperature dependence with maximum values between 20 and 30 °C. Comparison of these equilibrium constants with those of homopolymers stressed the unique character of the mitochondrial presequence. The findings are discussed in relation to the molecular recognition events at different stages of the transport process of this protein into mitochondria. [source] , -Peptide Conjugates: Syntheses and CD and NMR Investigations of ,/, -Chimeric Peptides, of a DPA- , -Decapeptide, and of a PEGylated , -HeptapeptideHELVETICA CHIMICA ACTA, Issue 12 2009James Gardiner Abstract ,3 -Peptides consisting of six, seven, and ten homologated proteinogenic amino acid residues have been attached to an , -heptapeptide (all d- amino acid residues; 4), to a hexaethylene glycol chain (PEGylation; 5c), and to dipicolinic acid (DPA derivative 6), respectively. The conjugation of the , -peptides with the second component was carried out through the N-termini in all three cases. According to NMR analysis (CD3OH solutions), the (M)- 314 -helical structure of the , -peptidic segments was unscathed in all three chimeric compounds (Figs.,2, 4, and 5). The , -peptidic section of the ,/, -peptide was unstructured, and so was the oligoethylene glycol chain in the PEGylated compound. Thus, neither does the appendage influence the , -peptidic secondary structure, nor does the latter cause any order in the attached oligomers to be observed by this method of analysis. A similar conclusion may be drawn from CD spectra (Figs.,1, 3, and 5). These results bode well for the development of delivery systems involving , -peptides. [source] NMR-Solution Structures of Fluoro-Substituted , -Peptides: A 314 -Helix and a Hairpin Turn.HELVETICA CHIMICA ACTA, Issue 12 2007-Fluoro-Amide Group, The First Case of a 90° OCCF Dihedral Angle in an Abstract To further study the preference of the antiperiplanar (ap) conformation in , -fluoro-amide groups, two , -peptides, 1 and 2, containing a (2-F)- ,3hAla and a (2-F)- ,2hPhe residue, have been synthesized. Their NMR-solution structures in CD3OH were determined and compared with those of non-F-substituted analogs, 3 and 4a. While we have found in a previous investigation (Helv. Chim. Acta2005, 88, 266) that a stereospecifically introduced F-substituent in the central position of a , - heptapeptide is capable of ,breaking' the 314 -helical structure by enforcing the FCCO ap -conformation, we could now demonstrate that the same procedure leads to a structure with the unfavorable ca. 90° FCCO dihedral angle, enforced by the 314 -helical folding in a , - tridecapeptide (cf.1; Fig.,4). This is interpreted as a consequence of cooperative folding in the longer , -peptide. A F-substituent placed in the turn section of a , -peptidic hairpin turn was shown to be in an ap -arrangement with respect to the neighboring CO bond (cf.2; Fig.,7). Analysis of the non-F-substituted , -tetrapeptides (with helix-preventing configurations of the two central ,2/,3 -amino acid residues) provides unusually tight hairpin structural clusters (cf.3 and 4a; Figs.,8 and 9). The skeleton of the , -tetrapeptide H-(R),3hVal-(R),2hVal-(R),3hAla-(S),3hPhe-OH (4a) is proposed as a novel, very simple backbone structure for mimicking , -peptidic hairpin turns. [source] Synthesis, CD Spectra, and Enzymatic Stability of ,2 -Oligoazapeptides Prepared from (S)-2-Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and LeuHELVETICA CHIMICA ACTA, Issue 12 2003Gérald Lelais , -Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs.,1 and 2). We report here the synthesis and spectroscopic investigations of ,2 -peptide analogs consisting of (S)-3-aza- , -amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N -benzyl- L - , -amino acids with an oxaziridine (Scheme,1). Couplings and fragment coupling of the 3-benzylaza- ,2 -amino acids and a corresponding tripeptide (N -Boc/C -OMe strategy) with common peptide-coupling reagents in solution led to ,2 -di, ,2 -tri-, and ,2 -hexaazapeptide derivatives, which could be N -debenzylated (4,9; Schemes,2,4). The new compounds were identified by optical rotation, and IR, 1H- and 13C-NMR, and CD spectroscopy (Figs.,4 and 5) and high-resolution mass spectrometry, and, in one case, by X-ray crystallography (Fig.,3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the ,2 -azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N -Boc and C -OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)- 314 -helical structure. The N -Boc- ,2 -tri and N -Boc- ,2 -hexaazapeptide esters, 7 and 9, were shown to be stable for 48,h against the following peptidases: pronase, proteinase,K, chymotrypsin, trypsin, carboxypeptidase,A, and 20S proteasome. [source] Liquid Crystals: Electrically Tuneable Liquid Crystal Photonic Bandgaps (Adv. Mater.ADVANCED MATERIALS, Issue 38-39 200939/2009) On p. 3915, Stephen Morris and co-workers demonstrate broadband wavelength tuning of a photonic bandgap that is electrically driven in a chiral nematic liquid crystal. Remarkably, this tuning is not only broadband but is found to occur without altering the reflection quality of the optical structure. In addition, under certain conditions, the helical structure can be made to exhibit multiple bandgaps across the visible spectrum. [source] Interaction of heparin with Ca2+: A model study with a synthetic heparin-like hexasaccharideISRAEL JOURNAL OF CHEMISTRY, Issue 3-4 2000Jesśs Angulo The binding of Ca2+ to synthetic hexasaccharide 1, containing the structural motifs of the regular region of heparin, has been investigated using NMR spectroscopy and molecular modeling. The NMR data of the calcium salt of 1 indicate the existence of specific Ca2+ binding, and molecular modeling results predict three different types of binding sites with different negative potential and preorganized geometry. The presence of Ca2+ does not seem to affect the overall helical structure of hexasaccharide 1, although it seems to have a marked influence on the flexibility of the oligosaccharide backbone. [source] Systematic epitope analysis of the p26 EIAV core proteinJOURNAL OF MOLECULAR RECOGNITION, Issue 4 2007Adriana Soutullo Abstract The major core protein of equine infectious anemia virus (EIAV), p26, is one of the primary immunogenic structural proteins during a persistent infection of horses and is highly conserved among antigenically variants of viral isolates. In order to investigate its immune profile in more detail for a better diagnostic, an epitope mapping was carried out by means of two libraries of overlapping peptide fragments prepared by simultaneous and parallel SPPS on derivatized cellulose membranes (SPOT synthesis). Polyclonal equine sera from infected horses were used for the biological assay. Particularly two promising continuous epitopes (NAMRHL and MYACRD) were localized on the C-terminal extreme of p26, region 194,222. A cyclic synthetic fragment of 29 amino acid residues containing the identified epitopes was designed and studied. A significant conformational change towards a helical structure was observed when the peptide was cyclized by a bridge between Cys198 and Cys218. This observation correlated with an improvement of its ability to be recognized by specific antibodies in an EIA (Enzyme-linked Immunosorbent assay). These results suggest that the conformationally restricted synthetic antigen adequately mimics the native structure of this region of p26 core protein. Copyright © 2007 John Wiley & Sons, Ltd. [source] Solution structure of LC5, the CCR5- derived peptide for HIV-1 inhibitionJOURNAL OF PEPTIDE SCIENCE, Issue 4 2010Kazuhide Miyamoto Abstract The synthetic peptide fragment (LC5: LRCRNEKKRHRAVRLIFTI) inhibits human immunodeficiency virus type 1 (HIV-1) infection of MT-4 cells. In this study, the solution structure of LC5 in SDS micelles was elucidated by using the standard 1H two-dimensional NMR spectroscopic method along with circular dichroism and fluorescence quenching. The peptide adopts a helical structure in the C-terminal region (residues 13,16), whereas the N-terminal part remains unstructured. The importance of Phe17 in maintaining the structure of LC5 was demonstrated by replacing Phe17 with Ala, which resulted in the dramatic conformational change of LC5. The solution structure of LC5 elucidated in the present work provides a basis for further study of the mechanism of the inhibition of HIV-1 infection. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Interaction of S413 -PV cell penetrating peptide with model membranes: relevance to peptide translocation across biological membranesJOURNAL OF PEPTIDE SCIENCE, Issue 5 2007Miguel Mano Abstract Cell penetrating peptides (CPPs) have been successfully used to mediate the intracellular delivery of a wide variety of molecules of pharmacological interest both in vitro and in vivo, although the mechanisms by which the cellular uptake occurs remain unclear and controversial. Following our previous work demonstrating that the cellular uptake of the S413 -PV CPP occurs mainly through an endocytosis-independent mechanism, we performed a detailed biophysical characterization of the interaction of this peptide with model membranes. We demonstrate that the interactions of the S413 -PV peptide with membranes are essentially of electrostatic nature. As a consequence of its interaction with negatively charged model membranes, the S413 -PV peptide becomes buried into the lipid bilayer, which occurs concomitantly with significant peptide conformational changes that are consistent with the formation of a helical structure. Comparative studies using two related peptides demonstrate that the conformational changes and the extent of cell penetration are dependent on the peptide sequence, indicating that the helical structure acquired by the S413 -PV peptide is relevant for its nonendocytic uptake. Overall, our data suggest that the cellular uptake of the S413 -PV CPP is a consequence of its direct translocation through cell membranes, following conformational changes induced by peptide-membrane interactions. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Simulation of the N -terminus of HIV-1 glycoprotein 41000 fusion peptide in micellesJOURNAL OF PEPTIDE SCIENCE, Issue 4 2005Allison Langham Abstract In this paper, the N -terminus of glycoprotein-41, the HIV-1 fusion peptide, was studied by molecular dynamics simulations in an explicit sodium dodecyl sulfate micelle. The simulation provides a detailed picture of the equilibrium structure and peptide stability as it interacts with the micelle. The equilibrium location of the peptide shows the peptide at the surface of the micelle with hydrophobic residues interacting with the micelle's core. At equilibrium, the peptide adopts an ,-helical structure from residues 5,16 and a type-1 ,-turn from 17,20 with the other residues exhibiting more flexible conformations. The primary hydrophobic interactions with the micelle are from the leucine and phenylalanine residues (Leu-7, Phe-8, Leu-9, Phe-11, Leu-12) while the alanine and glycine residues (Ala-1, Gly-3, Gly-5, Ala-6, Gly-10, Gly-13, Ala-14, Ala-15, Gly-16, Gly-10, Ala-21) interact favorably with water molecules. The results suggest that Phe-8, part of the highly conserved FLG motif of the fusion peptide, plays a key role in the interaction of the peptide with membranes. Our simulations corroborate experimental investigations of the fusion peptide in SDS micelles, providing a high-resolution picture that explains the experimental findings. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Structure,activity relationship of an antibacterial peptide, maculatin 1.1, from the skin glands of the tree frog, Litoria genimaculataJOURNAL OF PEPTIDE SCIENCE, Issue 7 2004Takuro Niidome Abstract Maculatin 1.1 (Mac) is a cationic antibacterial peptide isolated from the dorsal glands of the tree frog, Litoria genimaculata, and has a sequence of GLFGVLAKVAAHVVPAIAEHF-NH2. A short peptide lacking the N -terminal two residues of Mac was reported to have no activity. To investigate the structure,activity relationship in detail, several analogs and related short peptides of Mac were synthesized. CD measurement showed that all the peptides took more or less an ,-helical structure in the presence of anionic lipid vesicles. Analogs which are more basic than Mac had strong antibacterial and hemolytic activities, while short peptides lacking one or two terminal residues exhibited weak or no activity. Outer and inner membrane permeabilization activities of the peptides were also reduced with shortening of the peptide chain. These results indicate that the entire chain length of Mac is necessary for full activity, and the basicity of the peptides greatly affects the activity. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] HP(2,9)-magainin 2(1,12), a synthetic hybrid peptide, exerts its antifungal effect on Candida albicans by damaging the plasma membraneJOURNAL OF PEPTIDE SCIENCE, Issue 4 2004Yoonkyung Park Abstract In our previous study, HP(2,9)-MA(1,12), HP-MA for short, a hybrid peptide incorporating residues 2,9 of Helicobacter pylori ribosomal protein L1 (HP) and residues 1,12 of magainin 2 (MA) was shown to have strong antibacterial activity. In this study the antifungal activity of HP-MA was evaluated using various fungi, and it was shown that the activity was increased when compared with the parent peptides. In order to investigate the fungicidal mechanism(s) of HP-MA its action against fungal cell membranes was examined by the potassium-release test, which showed that HP-MA caused an increase in the amount of K+ released from the cells. Furthermore, HP-MA induced significant morphological changes. These facts suggested that the fungicidal effect of HP-MA involves damaging the fungal cell membranes. CD investigators suggested that the ,-helical structure of these peptides plays an important role in their antibiotic effect, but that ,-helicity is less directly correlated with the enhanced antibiotic activity of the hybrid. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Crystal-state 3D-structural characterization of novel 310 -helical peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 10 2003Dr Marco Crisma Abstract The crystal-state conformations of two octapeptides, pBrBz-(D -Iva)8 -OtBu (8I) and Ac-[L -(,Me)Val]8 -OH (8II), the heptapeptide Z-[L -(,Me)Val]7 -OH (7), the hexapeptide Z-[L -(,Me)Leu]6 -OtBu (6) and the tetrapeptide alkylamide Z-(Aib)2 - L -Glu(OMe)- L -Ala- L -Lol (5) were assessed by x-ray diffraction analyses. Two independent molecules are observed in the asymmetric unit of each L -(,Me)Val homo-peptide. All four homo-peptides are folded in a regular 310 -helical structure (only the C -terminal H-bonded conformation of the D -Iva octapeptide is distorted to a type-I ,-turn). The hydroxyl groups of the C -terminal carboxyl moieties of the two L -(,Me)Val homo-peptides participate in an oxy-analogue of the type-III ,-turn conformation. While the two L -(,Me)Val 310 -helices are right-handed, the D -Iva and L -(,Me)Leu helices are left-handed. The tetrapeptide alkylamide is 310 -helical at the N -terminus, but it is mixed 310/,-helical at the C -terminus. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Oligopeptide-mediated helix stabilization of model peptides in aqueous solutionJOURNAL OF PEPTIDE SCIENCE, Issue 2 2003Yoshitaka Maeda Abstract Oligopeptide-mediated helix stabilization of peptides in hydrophobic solutions was previously found by NMR and CD spectroscopic studies. The oligopeptide included the hydrophobic amino acids found in its parent peptide and were interposed by relevant basic or acidic amino acids. The strength of the interactions depended on the amino acid sequences. However, no helix-stabilizing effect was seen for the peptides in phosphate buffer solution, because the peptides assumed a random-coil structure. In order to ascertain whether the helix-stabilizing effect of an oligopeptide on its parent peptide could operate in aqueous solution, model peptides EK17 (Ac-AEAAAAEAAAKAAAAKA-NH2) and IFM17 (Ac-AEAAAAEIFMKAAAAKA-NH2) that may assume an ,-helix in aqueous solutions were synthesized. Interactions were examined between various oligopeptides (EAAAK, KAAAE, EIFMK, KIFME, KIFMK and EYYEE) and EK17 or IFM17 in phosphate buffer and in 80% trifluoroethanol (TFE),20% H2O solutions by CD spectra. EAAAK had little effect on the secondary structures of EK17 in both buffer and TFE solutions, while KAAAE, which has the reverse amino acid sequence of EAAAK, had a marked helix-destabilizing effect on EK17 in TFE. EIFMK and KIFME were found to stabilize the ,-helical structure of EK17 in phosphate buffer solutions, whereas KIFMK and EYYEE destabilized the ,-helical structure of EK17. EIFMK and KIFME had no effect on IFM17, because unexpectedly, IFM17 had appreciable amounts of ,-sheet structure in buffer solution. It was concluded that in order for the helix-stabilizing effects to operate effectively, the following factors should be satisfied: (1) the model peptide, the ,-helical conformation of which is to be stabilized, should essentially assume an ,-helical structure by nature, and (2) the hydrophobicity of the side-chains of the oligopeptide should be high enough for the oligopeptide to perform stable specific side chain,side chain intermolecular hydrophobic interactions with the model peptide. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Parallel and antiparallel dimers of magainin 2: their interaction with phospholipid membrane and antibacterial activityJOURNAL OF PEPTIDE SCIENCE, Issue 10 2002Yasuhiro Mukai Abstract Magainin 2 (M2) forms pores by associating with several other M2 molecules in lipid membranes and shows antibacterial activity. To examine the effect of M2 dimerization on biological activity and membrane interaction, parallel and antiparallel M2 dimers were prepared from two monomeric precursors. Antibacterial and haemolytic activities were enhanced by dimerization. CD measurements showed that both dimers and monomers have an ,-helical structure in the presence of lipid vesicles. Tryptophan fluorescence shift and KI quenching studies showed that all the peptides were more deeply embedded in acidic liposomes than in neutral liposomes. Experiments on dye-leakage activity and membrane translocation of peptides suggest that dimers and monomers form pores through lipid membranes, although the pore formation may be accompanied by membrane disturbance. Although dimerization of M2 increased the interaction activity with lipid membranes, no appreciable difference between the activities of parallel and antiparallel M2 dimers was observed. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Investigation of penetratin peptides Part 1.JOURNAL OF PEPTIDE SCIENCE, Issue 4 2002The environment dependent conformational properties of penetratin, two of its derivatives Abstract The homeodomain, the DNA-binding domain of Antennapedia homeoprotein, is composed of three ,-helices and one ,-turn between helices II and III. Its third helix from the N -terminal (helix III) can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. To the best of our knowledge, this helix III, called penetratin, which consists of 16 amino acids, is internalized by cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, the structure of penetratin was examined in both extracellular matrix-mimetic and membrane-mimetic environments; 1H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. The molecular conformations of two analogue peptides [(6,14-Phe)-penetratin and a 12 amino acid penetratin derivative (peptide 3)] were also studied. An atomic level comprehensive analysis of penetratin and its two analogues was performed. In a membrane-mimetic solvent system (TFEd2/water = 9 : 1), on the basis of 553 distance restraints, the 4,12 region of penetratin exhibits a bent, irregular helical structure on NMR examination. Interactions between hydrophobic amino acid residues in conjunction with H-bonds stabilize the secondary structure of the molecule. Thus, both derivatives adopt a helix-like conformation. However, while (6,14-Phe)-penetratin displays both ,-helical and 310 -helical features, the structure of peptide 3 is predominantly a 310 -helix. Of the three peptides, surprisingly (6,14-Phe)-penetratin has the largest helical content. An increase in the polarity of the molecular environment gradually disintegrates these helix-like secondary structures. In a highly aqueous molecular system (TFEd2/water = 1 : 9), the fast exchange of multiple conformers leads to too few distance restraints being extracted, therefore the NMR structures can no longer be determined. The NMR data show that only short-range order can be traced in these peptides. Under these conditions, the molecules adopt nascent helix-like structures. On the other hand, CD spectra could be recorded at any TFE/water ratio and the conformational interconversion could therefore be monitored as a function of the polarity of the molecular environment. The CD data were analysed comprehensively by the quantitative deconvolution method (CCA+). All three penetratin peptides display helical conformational features in a low dielectric medium, with significant differences as a function of their amino acid composition. However, these conformational features are gradually lost during the shift from an apolar to a polar molecular environment. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] SEQUENCE AND STRUCTURAL ANALYSIS OF ,-CARRAGEENAN-DERIVED OLIGOSACCHARIDES BY TWO-DIMENSIONAL NUCLEAR MAGNETIC RESONANCE,JOURNAL OF PHYCOLOGY, Issue 4 2010Wei Zhang ,-Carrageenan was hydrolyzed with mild hydrochloric acid and separated into a series of oligosaccharides, the sequences and structures of which were investigated by double-quantum filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), heteronuclear multiple-quantum coherence (HMQC), and heteronuclear multiple-bond correlation (HMBC) techniques, respectively. The chemical structures and conformations of the individual sugar residues were identified, as well as the sequential connectivity of the oligosaccharides. The interresidue nuclear Overhauser effects (NOEs)/rotating frame Overhauser effects (ROEs) revealed an ordered helical structure of the carrageenan oligosaccharide chains. Therefore, a general two-dimensional (2-D) NMR methodology for the unambiguous sequence and structure analysis of ,-carrageenan-derived oligosaccharides was established in this study. [source] Development of synthetic double helical polymers and oligomersJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 20 2009Yoshio Furusho Abstract There is growing interest in the design and synthesis of artificial helical polymers and oligomers, in connection with biological importance as well as development of novel chiral materials. Since the discovery of the helical structure of isotactic polypropylene, a significant advancement has been achieved for synthetic polymers and oligomers with a single helical conformation for about half a century. In contrast, the chemistry of double helical counterparts is still premature. This short review highlights the recent advances in the synthesis, structures, and functions of double helical polymers and oligomers, featuring an important role of supramolecular chemistry in the design and synthesis of double helices. Although the artificial double helices reported to date are still limited in number, recent advancement of supramolecular chemistry provides plenty of structural motifs for new designs. Therefore, artificial double helices hold great promise as a new class of compounds. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5195,5207, 2009 [source] Side-chain supramolecular polymers with induced supramolecular chirality through H-bonding interactionsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 16 2008Francisco Vera Abstract Side-chain supramolecular polymers that show columnar mesomorphism have been prepared through H-bonding interactions between a polyvinylpyridine polymer as H-acceptor and different H-donors derived from benzoic acid. These compounds have been designed according to a promesogenic structure, that is, either disk-like or banana-like, to promote stacking and therefore the formation of columnar arrangements. IR studies confirmed the formation of H-bonds and demonstrated that the H-bond intensity decreases upon increasing temperature. The mesophase organizations were studied by polarized optical microscopy, differential scanning calorimetry, and X-ray diffraction. Associations containing poly-3-methyl-4-vinylpyridine showed supramolecular optical activity, as evidenced by circular dichroism studies on thin films. It is proposed that these supramolecular polymers adopt a helical structure that can be biased toward a given handedness by virtue of the configuration of the stereogenic centers in the peripheral tails of the acids. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5528,5541, 2008 [source] Self-assembly of supramolecular polymers into tunable helical structuresJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 6 2008Ho-Joong Kim Abstract There is growing interest in the design of synthetic molecules that are able to self-assemble into a polymeric chain with compact helical conformations, which is analogous to the folded state of natural proteins. Herein, we highlight supramolecular approach to the formation of helical architectures and their conformational changes driven by external stimuli. Helical organization in synthetic self-assembling systems can be achieved by the various types of noncovalent interactions, which include hydrogen bonding, solvophobic effects, and metal-ligand interactions. Since the external environment can have a large influence on the strength and configuration of noncovalent interactions between the individual components, stimulus-induced alterations in the intramolecular noncovalent interactions can result in dynamic conformational change of the supramolecular helical structure thus, driving significant changes in the properties of the materials. Therefore, these supramolecular helices hold great promise as stimuli-responsive materials. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1925,1935, 2008 [source] Synthesis and chiroptical properties of optically active poly(ethynylcarbazole) derivatives: Substituent effect on the helix formationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2007Fumio Sanda Abstract Novel chiral acetylene monomers containing carbazole, 2-ethynyl-9-[(S)-2-methylbutoxycarbonyl]carbazole (1), 3-ethynyl-9-[(S)-2-methylbutoxycarbonyl]carbazole (2), 2-ethynyl-9-[(S)-2-methylbutyl]carbazole (3), and 2-ethynyl-9-[(S)-4-methylhexyl]carbazole (4) were synthesized and polymerized with [(nbd)RhCl]2Et3N. The corresponding polyacetylenes with number-average molecular weights ranging from 68,700 to 310,000 were obtained in good yields. Poly(1) exhibited a large specific rotation and an intense Cotton effect in toluene, indicating that it formed a helix with predominantly one-handed screw sense, while the other three polymers showed no evidence for taking a helical structure. Poly(1) largely decreased the CD intensity upon heating from ,10 to 60 °C. Poly(1) showed a Cotton effect in film state in a manner similar to solution state. No chiral amplification was observed in the copolymerization of 1 with achiral 2-ethynyl-9- tert -butoxycarbonylcarbazole (5). © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4450,4458, 2007 [source] | |||||||||||||||||||||||||||||||||||||