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Lead Structures (lead + structure)
Kinds of Lead Structures Selected AbstractsEfficiency enhancement of 400 nm violet LEDs utilizing island-like GaN thick film by HVPE technologyPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 1 2007Jenq-Dar Tsay Abstract In this study, we develop a novel way to fabricate InGaN/GaN LED chips with special shape for improving the output power. Crack-free shaped GaN islands were first prepared on c-axis sapphire substrate by using HVPE selective area growth. By doing so, GaN islands with flat top surface and inclined side faces are obtained. Then, the InGaN/GaN LED structure was grown on the top surface of the GaN island subsequently. The output powers of the p-side up and the p-side down shaped LED chip are 1.4 and 2.2 times the output power of the cubic chip, respectively. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Comparative study between laser performance and carrier lifetime of 400 nm emitting GaInN/GaN laser diodesPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 7 2003C. Netzel Abstract GaInN/GaN laser diodes with different laser performance but nearly identical structural design, all emitting at around 400 nm, were investigated with time-resolved and temperature-dependent photoluminescence under pulsed excitation and with temperature- and power-dependent photoluminescence under cw excitation. To compare the laser diodes with LEDs, the same measurements were performed for an LED structure emitting in the same spectral region. The time-resolved photoluminescence as well as the measurements under continuous excitation point at a more efficient nonradiative recombination for laser structures. This enhancement of nonradiative recombination for the laser diodes was observed to be most pronounced for the best laser diodes. (© 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] GaN nanorods and LED structures grown on patterned Si and AlN/Si substrates by selective area growthPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 7-8 2010Shunfeng Li Abstract GaN nanorods (NRs) show promising applications in high-efficiency light emitting diodes, monolithic white light emission and optical interconnection due to their superior properties. In this work, we performed GaN nanostructures growth by pre-patterning the Si and AlN/Si substrates. The pattern was transferred to Si and AlN/Si substrates by photolithography and inductively-coupled plasma etching. GaN NRs were grown on these templates by metal-organic vapour phase epitaxy (MOVPE). GaN grown on Si pillar templates show a truncated pyramidal structure. Transmission electron microscopy measurements demonstrated clearly that the threading dislocations bend to the side facets of the GaN nanostructures and terminate. GaN growth can also be observed on the sidewalls and bottom surface between the Si pillars. A simple phenomenological model is proposed to explain the GaN nanostructure growth on Si pillar templates. Based on this model, we developed another growth method, by which we grow GaN rod structures on pre-patterned AlN/Si templates. By in-situ nitridation and decreasing of the V/III ratio, we found that GaN rods only grew on the patterned AlN/Si dots with an aspect ratio of about 1.5 - 2. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Morphological study of non-polar (11-20) GaN grown on r-plane (1-102) sapphirePHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 6 2008C. F. Johnston Abstract In order to grow high quality non-polar GaN-based LED structures it is important to understand the mechanism of GaN growth by MOVPE on r-plane (1-102) sapphire. In this work, (11-20) GaN epilayers have been characterised at three stages of growth using high resolution X-ray diffraction (HRXRD), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Following nucleation, 3D islands were grown, then the V/III ratio was lowered and the islands coalesced to form a smooth film. A series of symmetric XRD ,-scans obtained at different azimuthal angles revealed an anisotropy in the layers with respect to the [1-100] and [0001] axes. AFM scans show that the islands are elongated along the [0001] axis. TEM has been used to analyse the layers further. A high density of stacking faults (5x105 cm,1) and threading dislocations (4x1010 cm,2) was found in the film with 120 s high V/III growth followed by low V/III growth. Defects were found to run perpendicular and at ,60 degrees to the sapphire interface in uncoalesced "island" samples. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Syntheses and Antibacterial Properties of iso -Platencin, Cl- iso -Platencin and Cl-Platencin: Identification of a New Lead StructureCHEMISTRY - A EUROPEAN JOURNAL, Issue 31 2010Konrad Tiefenbacher Dr. Abstract Platencin is a novel antibiotic which is active against multiresistant pathogens. We describe efficient syntheses of three platencin analogues of varying activities which allow further conclusions about the pharmacophoric part of the molecule. The unnatural antibiotic iso -platencin, which is about as active as natural platencin, but much more selective, was identified as a new lead structure. [source] Cyanopeptide Analogues: New Lead Structures for the Design and Synthesis of New Thrombin Inhibitors.CHEMINFORM, Issue 7 2003G. Radau Abstract For Abstract see ChemInform Abstract in Full Text. [source] Can [M(H)2(H2)(PXP)] Pincer Complexes (M=Fe, Ru, Os; X=N, O, S) Serve as Catalyst Lead Structures for NH3 Synthesis from N2 and H2?CHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2007Markus Hölscher Dr. Abstract The potential of pincer complexes [M(H)2(H2)(PXP)] (M=Fe, Ru, Os; X=N, O, S) to coordinate, activate, and thus catalyze the reaction of N2 with classical or nonclassical hydrogen centers present at the metal center, with the aim of forming NH3 with H2 as the only other reagent, was explored by means of DF (density functional) calculations. Screening of various complexes for their ability to perform initial hydrogen transfer to coordinated N2 showed ruthenium pincer complexes to be more promising than the corresponding iron and osmium analogues. The ligand backbone influences the reaction dramatically: the presence of pyridine and thioether groups as backbones in the ligand result in inactive catalysts, whereas ether groups such as ,-pyran and furan enable the reaction and result in unprecedented low activation barriers (23.7 and 22.1,kcal,mol,1, respectively), low enough to be interesting for practical application. Catalytic cycles were calculated for [Ru(H)2(H2)(POP)] catalysts (POP=2,5-bis(dimethylphosphanylmethyl)furan and 2,6-bis(dimethylphosphanylmethyl)-,-pyran). The height of activation barriers for the furan system is somewhat more advantageous. Formation of inactive metal nitrides has not been observed. SCRF calculations were used to introduce solvent (toluene) effects. The Gibbs free energies of activation of the numerous single reaction steps do not change significantly when solvent is included. The reaction steps associated with the formation of the active catalyst from precursors [M(H)2(H2)(PXP)] were also calculated. The otherwise inactive pyridine ligand system allows for the generation of the active catalyst species, whereas the ether ligand systems show activation barriers that could prohibit practical application. Consequently the generation of the active catalyst species needs to be addressed in further studies. [source] Synthesis and Biological Evaluation of Pretubulysin and Derivatives,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 36 2009Angelika Ullrich Abstract Pretubulysin, a biosynthetic precursor of the tubulysins, shows potent biological activity in the subnanomolar range towards various tumor cell lines. Its activity is only slightly less than those of the structurally more complex tubulysins. With a straightforward synthesis to hand, pretubulysin is an ideal lead structure for the development of tubulysin-based anticancer drugs(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis of cyclooctapeptides: constraints analogues of the peptidic neurotoxin, ,-agatoxine IVB,an experimental point of viewJOURNAL OF PEPTIDE SCIENCE, Issue 3 2008Ewelina Minta Abstract ,-AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q-type calcium channels. The best route to achieve the analogues possessing the three-dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza-tryptophane and alanine were synthesized. The synthesis was carried out on various acid-labile resins (BARLOS chlorotrityl, Rink amide, PEG-based or Wang resins), by Fmoc strategy. In this paper, we describe optimization of the peptide cyclization with various protecting groups, and on resin or in solution cyclization experimental parameters. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] QSAR Analysis of 2,3-Diaryl Benzopyrans/Pyrans as Selective COX-2 Inhibitors Based on Semiempirical AM1 CalculationsMOLECULAR INFORMATICS, Issue 8 2004Sivaprakasam Prasanna Abstract Quantitative structure-activity relationship (QSAR) analysis was performed on a combined series of 2,3 diaryl benzopyrans and pyrans for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations based on semiempirical, Austin Model-1 (AM1) calculations reveal that electronic and hydophobic interactions are primarily responsible for COX-2 enzyme-ligand interaction. The derived QSAR model aided by residual analysis demonstrated that the COX-2 inhibitory activity is highly correlated with the electronic descriptors, lowest unoccupied molecular orbital (ELUMO), Dipole-Z and hydrophobicity of the molecules. The conclusion can be drawn that more hydrophobic, electron-withdrawing substituents at 3rd aromatic ring of the lead structure improves activity. The lesser the Z component the ligand has, the more correct its orientation towards the COX-2 binding site. The derived QSAR model shows good internal (exemplified through leave one out-q2=0.786) and external (r=0.5737) predictive ability for a test set and can be used in designing better selective COX-2 inhibitors among these congeners in future. [source] Synthesis of Dimeric Quinazolin-2-one, 1,4-Benzodiazepin-2-one, and Isoalloxazine Compounds as Inhibitors of Amyloid Peptides AssociationARCHIV DER PHARMAZIE, Issue 8 2009Alexander Barthel Abstract The synthesis of dimeric compounds derived from quinazolin-2-one and 1,4-benzodiazepin-2-one possessing a piperazine or homopiperazine spacer was investigated. In addition, a piperazine spacered bis-isoalloxazine and a bis-riboflavin compound were prepared and their ability to interrupt the association of prion proteins and Alzheimer-specific A, peptides was investigated using a fast screening system based on flow cytometry. The bis-isoalloxazine 14 was identified as a new lead structure. [source] Syntheses and Antibacterial Properties of iso -Platencin, Cl- iso -Platencin and Cl-Platencin: Identification of a New Lead StructureCHEMISTRY - A EUROPEAN JOURNAL, Issue 31 2010Konrad Tiefenbacher Dr. Abstract Platencin is a novel antibiotic which is active against multiresistant pathogens. We describe efficient syntheses of three platencin analogues of varying activities which allow further conclusions about the pharmacophoric part of the molecule. The unnatural antibiotic iso -platencin, which is about as active as natural platencin, but much more selective, was identified as a new lead structure. [source] Characterization of New PPAR, Agonists: Analysis of Telmisartan's Structural ComponentsCHEMMEDCHEM, Issue 3 2009Matthias Goebel Abstract Telmisartan was originally designed as an AT1 antagonist but was later also characterized as a selective PPAR, modulator. This study focused on the identification of the essential structural motifs of telmisartan for PPAR, activation activity, elucidating the individual SAR of each different component (shown). In addition to a proven efficacy in lowering blood pressure, the AT1 receptor blocker telmisartan has recently been shown to exert pleiotropic effects as a partial agonist of the nuclear peroxisome proliferator-activated receptor gamma (PPAR,). Based on these findings and an excellent side-effect profile, telmisartan may serve as a lead structure for the development of new PPAR, ligands. Therefore, we analyzed the structural components of telmisartan to identify those necessary for PPAR, activation. Synthesized compounds were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay with COS-7 cells transiently transfected with pGal4-hPPAR,DEF, pGal5-TK-pGL3 and pRL-CMV. The data obtained in this structure,activity relationship (SAR) study provide the basis for the development of new PPAR, ligands, which could lead to active compounds with a distinct, beneficial pharmacological profile compared with the existing full agonists. The basic 1-(biphenyl-4-ylmethyl)-1H -benzimidazole scaffold of telmisartan was identified as an essential moiety with either a carboxylic acid or tetrazole group at the C-2 position of the biphenyl. For maximum potency and activity, the alkyl chain in position 2 requires a minimum length of at least two C atoms (ethyl group), while the methyl group at position 4 of the benzimidazole core seems to contribute to partial activity. An additional benzimidazole at position 6 appears to be a further determinant of potency. Similar conclusions can be drawn for the methyl group in position 1. [source] Site-directed mutagenesis of the active site serine290 in flavanone 3,-hydroxylase from Petunia hybridaFEBS JOURNAL, Issue 3 2000Richard Luka Flavanone 3,-hydroxylase (FHT) catalyzes a pivotal reaction in the formation of flavonoids, catechins, proanthocyanidins and anthocyanidins. In the presence of oxygen and ferrous ions the enzyme couples the oxidative decarboxylation of 2-oxoglutarate, releasing carbon dioxide and succinate, with the oxidation of flavanones to produce dihydroflavonols. The hydroxylase had been cloned from Petunia hybrida and expressed in Escherichia coli, and a rapid isolation method for the highly active, recombinant enzyme had been developed. Sequence alignments of the Petunia hydroxylase with various hydroxylating 2-oxoglutarate-dependent dioxygenases revealed few conserved amino acids, including a strictly conserved serine residue (Ser290). This serine was mutated to threonine, alanine or valine, which represent amino acids found at the corresponding sequence position in other 2-oxoglutarate-dependent enzymes. The mutant enzymes were expressed in E. coli and purified to homogeneity. The catalytic activities of [Thr290]FHT and [Ala290]FHT were still significant, albeit greatly reduced to 20 and 8%, respectively, in comparison to the wild-type enzyme, whereas the activity of [Val290]FHT was negligible (about 1%). Kinetic analyses of purified wild-type and mutant enzymes revealed the functional significance of Ser290 for 2-oxoglutarate-binding. The spatial configurations of the related Fe(II)-dependent isopenicillin N and deacetoxycephalosporin C synthases have been reported recently and provide the lead structures for the conformation of other dioxygenases. Circular dichroism spectroscopy was employed to compare the conformation of pure flavanone 3,-hydroxylase with that of isopenicillin N synthase. A double minimum in the far ultraviolet region at 222 nm and 208,210 nm and a maximum at 191,193 nm which are characteristic for ,-helical regions were observed, and the spectra of the two dioxygenases fully matched revealing their close structural relationship. Furthermore, the spectrum remained unchanged after addition of either ferrous ions, 2-oxoglutarate or both of these cofactors, ruling out a significant conformational change of the enzyme on cofactor-binding. [source] Cover Picture: Targeting RNA with Small Molecules (ChemBioChem 10/2003)CHEMBIOCHEM, Issue 10 2003Yitzhak Tor Prof. Dr. Abstract The cover picture shows the processes involved in the search for small molecules as potent and selective RNA binders. Motivation comes from the desire to control cell function at the RNA level and to identify novel approaches to specifically combat pathogens by targeting their unique RNA sequences or RNA,protein complexes. Inspiration comes from nature; in particular, from aminoglycosides, a family of naturally occurring antibiotics that has been shown to target the bacterial ribosome. The discovery process involves identifying RNA targets (schematically shown as a ribosome or a virus), devising unique assays (e.g. a solid-phase assay), and generating the necessary knowledge and lead structures through design, synthesis, and systematic evaluation of biological activity. Further details can be found in the article by Y. Tor on p. 998 ff. [source] New indolicidin analogues with potent antibacterial activity,CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2004T.S. Ryge Abstract:, Indolicidin is a 13-residue antimicrobial peptide amide, ILPWKWPWWPWRR-NH2, isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is active against a wide range of microorganisms and has also been shown to be haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of the present paper is two-fold. First, we examine the importance of tryptophan in the antibacterial activity of indolicidin. We prepared five peptide analogues with the format ILPXKXPXXPXRR-NH2 in which Trp-residues 4,6,8,9,11 were replaced in all positions with X = a single non-natural building block; N -substituted glycine residue or nonproteinogenic amino acid. The analogues were tested for antibacterial activity against both Staphylococcus aureus American type culture collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan is not essential in the antibacterial activity of indolicidin, and even more active analogues were obtained by replacing tryptophan with non-natural aromatic amino acids. Using this knowledge, we then investigated a new principle for improving the antibacterial activity of small peptides. Our approach involves changing the hydrophobicity of the peptide by modifying the N-terminus with a hydrophobic non-natural building block. We prepared 22 analogues of indolicidin and [Phe4,6,8,9,11] indolicidin, 11 of each, carrying a hydrophobic non-natural building block attached to the N-terminus. Several active antibacterial analogues were identified. Finally, the cytotoxicity of the analogues against sheep erythrocytes was assessed in a haemolytic activity assay. The results presented here suggest that modified analogues of antibacterial peptides, containing non-natural building blocks, are promising lead structures for developing future therapeutics. [source] Wirkstoffe auf Basis biologisch aktiver NaturstoffeCHEMIE IN UNSERER ZEIT (CHIUZ), Issue 5 2007Jörg Heilmann Prof. Dr. Im Bereich der Wirkstoffsuche sind Naturstoffe unverzichtbar. Problematisch bei der Gewinnung von Naturstoffen sind die Beschaffung des biologischen Materials, die Auffindung und Isolierung aus einer inaktiven oder sogar die biologische Testung störenden Matrix und die Gewinnung ausreichender Mengen zur chemischen und pharmakologischen Charakterisierung bzw. für die klinische Nutzung. Oft stellen Naturstoffe ideale Leitstrukturen für die synthetische oder semisynthetische Entwicklung von Wirkstoffen dar. Besonders attraktiv sind Naturstoffe dann, wenn die biologische Quelle erneuerbar bzw. sogar in Kultur modifizierbar ist. Dies ist ein wesentlicher Aspekt für die gegenwärtige Attraktivität der Wirkstoffsuche in Mikroorganismen wie Bakterien und Pilzen. Diese können im Idealfall nicht nur in Fermentern kultiviert, sondern dort auch genetisch so verändert werden, dass neuartige Strukturen entstehen. The potential of natural products as sources for new drugs and lead structures is still largely unexplored and due to their unmatched structural diversity, secondary natural products continue to play a highly significant role in drug discovery. This article gives an overview on different strategies, chemical and biological methods as well as limiting problems for the search, screening, isolation and characterization of bioactive natural products from different sources. Ecological aspects and the importance of biodiversity and sustainable sourcing are also discussed. [source] ChemInform Abstract: Derivatives of Benzimidazole Pharmacophore: Synthesis, Anticonvulsant, Antidiabetic and DNA Cleavage Studies.CHEMINFORM, Issue 33 2010Ramya V. Shingalapur Abstract A group of 1,3,4-oxadiazoles and 4-thiazolidinones containing a 2-mercapto-benzimidazole moiety is synthesized and screened for new lead structures. [source] TMC-95A Analogues with Endocyclic Biphenyl Ether Group as Proteasome InhibitorsCHEMISTRY & BIODIVERSITY, Issue 1 2004Markus Kaiser TMC-95A, a cyclic tripeptide metabolite of Apiospora montagnei, is a potent competitive inhibitor of proteasome. Based on the X-ray structure of its complex with yeast proteasome, the synthetically challenging structure of this natural product was simplified in a first generation of analogues by replacing the highly oxidized side-chain biaryl system with a phenyl-oxindole group. In the present study, the TMC-95 biaryl group was substituted with a biphenyl ether with retainment of significant proteasome inhibition. Because of the facile synthetic access of tripeptides containing in i, i+2 positions residues of the isodityrosine type, this new generation of TMC-95 analogues may represent promising lead structures for further optimization of affinity and selectivity of proteasome inhibitors. [source] Total Synthesis and Initial Structure,Activity Relationships of Longicatenamycin,ACHEMMEDCHEM, Issue 4 2008Franz von, Nussbaum Dr. Abstract Natural products have provided the majority of lead structures for marketed antibacterials. In addition, they are biological guide principles to new therapies. Nevertheless, numerous "old" classes of antibiotics such as the longicatenamycins have never been explored by chemical postevolution. Longicatenamycin,A is the first defined longicatenamycin congener that has been totally synthesized and tested in pure form. This venture required the de,novo syntheses of the non-proteinogenic amino acids (2S,3R)-,-hydroxyglutamic acid (HyGlu), 5-chloro- D -tryptophan (D -ClTrp), and (S)-2-amino-6-methylheptanoic acid (hhLeu). In the key step, the sensitive HyGlu building block was coupled as a pentafluorophenyl active ester to the unprotected H- D -ClTrp-Glu-hhLeu- D -Val- D -(Cbz)Orn-OH fragment. This first total synthesis of longicatenamycin,A provided new congeners of the natural product (deacetyllongicatenamycin, dechlorolongicatenamycin, and longicatenamycin-A-amide). [source] | ||||||||||||||||||||||||||||