bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Inverse Substrate Orientation for the Regioselective Acylation of 3′,5′‐Diaminonucleosides Catalyzed by Candida antarctica lipase B?
Authors: Lavandera Iván , Fernández Susana , Magdalena Julia , Ferrero Miguel , Kazlauskas Romas J. , Gotor Vicente 
Published: June 2005

AbstractCandida antarctica lipase B (CAL‐B) catalyzes the regioselective acylation of natural thymidine with oxime esters and also the regioselective acylation of an analogue, 3′,5′‐diamino‐3′,5′‐dideoxythymidine with nonactivated esters. In both cases, acylation favors the less hindered 5′‐position over the 3′‐position by upto 80‐fold. Computer modeling of phosphonate transition‐state analogues for the acylation of thymidine suggests that CAL‐B favors acylation of the 5′‐position because this orientation allows the thymine ring to bind in a hydrophobic pocket and forms stronger key hydrogen bonds than acylation of the 3′‐position. On the other hand, computer modeling of phosphonamidate analogues of the transition states for acylation of either the 3′‐ or 5′‐amino groups in 3′,5′‐diamino‐3′,5′‐dideoxythymidine shows similar orientations and hydrogen bonds and, thus, does not explain the high regioselectivity. However, computer modeling of inverse structures, in which the acyl chain binds in the nucleophile pocket and vice versa, does rationalize the observed regioselectivity. The inverse structures fit the 5′‐, but not the 3′‐intermediate thymine ring, into the hydrophobic pocket, and form a weak new hydrogen bond between the O‐2 carbonyl atom of the thymine and the nucleophile amine only for the 5′‐intermediate. A water molecule might transfer a proton from the ammonium group to the active‐site histidine. As a test of this inverse orientation, we compared the acylation of thymidine and 3′,5′‐diamino‐3′,5′‐dideoxythymidine with butyryl acyl donors and with isosteric methoxyacetyl acyl donors. Both acyl donors reacted at equal rates with thymidine, but the methoxyacetyl acyl donor reacted four times faster than the butyryl acyl donor with 3′,5′‐diamino‐3′,5′‐dideoxythymidine. This faster rate is consistent with an inverse orientation for 3′,5′‐diamino‐3′,5′‐dideoxythymidine, in which the ether oxygen atom of the methoxyacetyl group can form a similar hydrogen bond to the nucleophilic amine. This combination of modeling and experiments suggests that such lipase‐catalyzed reactions of apparently close substrate analogues like alcohols and amines might follow different pathways.
Chemical Synthesis of a Dual Branched Malto‐Decaose: A Potential Substrate for α‐Amylases
Authors: Damager Iben , Jensen Morten T. , Olsen Carl E. , Blennow Andreas , Møller Birger L. , Svensson Birte , Motawia Mohammed S. 
Published: June 2005

AbstractA convergent block strategy for general use in efficient synthesis of complex α‐(1→4)‐ and α‐(1→6)‐malto‐oligosaccharides is demonstrated with the first chemical synthesis of a malto‐oligosaccharide, the decasaccharide 6,6′′′′‐bis(α‐maltosyl)‐maltohexaose, with two branch points. Using this chemically defined branched oligosaccharide as a substrate, the cleavage pattern of seven different α‐amylases were investigated. α‐Amylases from human saliva, porcine pancreas, barley α‐amylase 2 and recombinant barley α‐amylase 1 all hydrolysed the decasaccharide selectively. This resulted in a branched hexasaccharide and a branched tetrasaccharide. α‐Amylases from Asperagillus oryzae, Bacillus licheniformis and Bacillus sp. cleaved the decasaccharide at two distinct sites, either producing two branched pentasaccharides, or a branched hexasaccharide and a branched tetrasaccharide. In addition, the enzymes were tested on the single‐branched octasaccharide 6‐α‐maltosyl‐maltohexaose, which was prepared from 6,6′′′′‐bis(α‐maltosyl)‐maltohexaose by treatment with malt limit dextrinase. A similar cleavage pattern to that found for the corresponding linear malto‐oligosaccharide substrate was observed.
LanGT2 Catalyzes the First Glycosylation Step during Landomycin A Biosynthesis
Authors: Luzhetskyy Andriy , Taguchi Takaaki , Fedoryshyn Marta , Dürr Clemens , Wohlert Sven‐Eric , Novikov Volodymyr , Bechthold Andreas 
Published: June 2005

AbstractThe glycosyltransferase LanGT2 is involved in the biosynthesis of the hexasaccharide side chain of the angucyclic antibiotic landomycin A. Its function was elucidated by targeted gene inactivation of lanGT2. The main metabolite of the obtained mutant was identified as tetrangulol (4), the progenitor of the landomycin aglycon (7). The lack of the sugar side chain indicates that LanGT2 catalyzes the priming glycosyl transfer in the hexasaccharide biosynthesis: the attachment of a D‐olivose to O‐8 of the polyketide backbone. Heterologous expression of urdGT2 from S. fradiae Tü2717 in this mutant resulted in the production of a novel C‐glycosylated angucycline (6).
Metabolic Engineering of Aminocoumarins: Inactivation of the Methyltransferase Gene cloP and Generation of New Clorobiocin Derivatives in a Heterologous Host
Authors: Freitag Anja , Rapp Heike , Heide Lutz , Li Shu‐Ming 
Published: June 2005

AbstractAminocoumarin antibiotics are highly potent inhibitors of bacterial gyrase and represent a class of antibiotics that are very suitable for the generation of new compounds by metabolic engineering. In this study, the putative methyltransferase gene cloP in the biosynthetic gene cluster of clorobiocin was inactivated. Expression of the modified gene cluster in the heterologous host Streptomyces coelicolor M512 gave three new aminocoumarin antibiotics. The structures of the new compounds were elucidated by MS and 1H NMR, and their antibacterial activities were determined. All three compounds lacked clorobiocin's methyl group at 4‐OH of the deoxysugar moiety, noviose. They differed from each other in the position of the 5‐methylpyrrole‐2‐carbonyl group, which was found to be attached to either 2‐OH, 3‐OH or 4‐OH of noviose. Attachment at 4‐OH resulted in the highest antibacterial activity. This is the first time that an aminocoumarin antibiotic acylated at 4‐OH in noviose has been detected.
An Enzyme Module System for the Synthesis of dTDP‐activated Deoxysugars from dTMP and Sucrose
Authors: Elling Lothar , Rupprath Carsten , Günther Nicole , Römer Ulrike , Verseck Stefan , Weingarten Petra , Dräger Gerald , Kirschning Andreas , Piepersberg Wolfgang 
Published: June 2005

AbstractA flexible enzyme module system is presented that allows preparative access to important dTDP‐activated deoxyhexoses from dTMP and sucrose. The strategic combination of the recombinant enzymes dTMP‐kinase and sucrose synthase (SuSy), and the enzymes RmlB (4,6‐dehydratase), RmlC (3,5‐epimerase) and RmlD (4‐ketoreductase) from the biosynthetic pathway of dTDP‐β‐L‐rhamnose was optimized. The SuSy module (dTMP‐kinase, SuSy, ±RmlB) yielded the precursor dTDP‐α‐D‐glucose (2) or the biosynthetic intermediate dTDP‐6‐deoxy‐4‐keto‐α‐D‐glucose (3) on a 0.2–0.6 g scale with overall yields of 62 % and 72 %, respectively. A two‐step strategy in which the SuSy module was followed by the deoxysugar module (RmlC and RmlD) resulted in the synthesis of dTDP‐β‐L‐rhamnose (4; 24.1 μmol, overall yield: 35.9 %). Substitution of RmlC by DnmU from the dTDP‐β‐L‐daunosamine pathway of Streptomyces peucetius in this module demonstrated that DnmU acts in vitro as a 3,5‐epimerase with 3 as substrate to yield 4 (32.2 μmol, overall yield: 44.7 %). Chemical reduction of 3 with NaBH4 gave a mixture of the C‐4 epimers dTDP‐α‐D‐quinovose (6) and dTDP‐α‐D‐fucose (7) in a ratio of 2:1. In summary, the modular character of the presented enzyme system provides valuable compounds for the biochemical characterization of deoxysugar pathways playing a major role in microbial producers of antibiotic and antitumour agents.
Oxidation States and CO Ligand Exchange Kinetics in a Self‐Assembled Monolayer of a Triruthenium Cluster Studied by In Situ Infrared Spectroscopy
Authors: Zhou Wei , Ye Shen , Abe Masaaki , Nishida Takuma , Uosaki Kohei , Osawa Masatoshi , Sasaki Yoichi 
Published: June 2005

AbstractOxidation states and CO ligand exchange kinetics in a self‐assembled monolayer (SAM) of an oxo‐centered triruthenium cluster [Ru3(μ3‐O)(μ‐CH3COO)6(CO)(L1)(L2)] (L1 = [(NC5H4)CH2NHC(O)(CH2)10S‐]2, L2 = 4‐methylpyridine) have been extensively investigated on the surface of a gold electrode in aqueous and nonaqueous solutions. The SAM exhibits three consecutive one‐electron transfers and four oxidation states, which have been characterized by electrochemistry, in situ infrared spectroscopy, and in situ sum frequency generation (SFG) vibrational spectroscopy measurements. The original electron‐localized state of the Ru cluster center was changed to electron delocalization states by oxidation or reduction of the central Ru ions. These changes are revealed by the IR absorptions of the CO ligand and the bridging acetate ligands of the triruthenium cluster in the SAM. The IR absorptions of the two kinds of ligands are strongly dependent on the oxidation state of the Ru cluster center. One‐electron oxidation of the central Ru ion in the SAM triggers a CO ligand liberation process. Solvent molecules may then occupy the CO site to result in a CO‐free SAM. One‐electron reduction of this CO‐free SAM in a CO‐saturated solution leads to re‐coordination of the CO ligand into the SAM. Both processes can be precisely controlled by tuning the electrode potential. The kinetics of the CO exchange cycle in the SAM, including liberation and coordination, has been investigated by in situ IR and SFG measurements for the first time. The CO exchange cycle is significantly dependent on the temperature. The reaction rate greatly decreases with decreasing solution temperature, which is an important factor in the CO ligand exchange process. The activation energies of both CO liberation and coordination have been evaluated from the reaction rate constants obtained at various temperatures.
Peptide Electron Transfer: More Questions than Answers
Authors: Long Yi‐Tao , Abu‐Irhayem Erfan , Kraatz Heinz‐Bernhard 
Published: June 2005

AbstractNature has specifically designed proteins, as opposed to DNA, for electron transfer. There is no doubt about the electron transfer within proteins compared with the uncertain and continuing debate about charge transfer through DNA. However, the exact mechanism of electron transfer within peptide systems has been a source of controversy. Two different mechanisms for electron transfer between a donor and an acceptor, electron hopping and bridge‐assisted superexchange, have been proposed, and are supported by experimental evidence and theoretical calculations. Several factors were found to affect the kinetics of this process, including peptide chain length, secondary structure and hydrogen bonding. Electrochemical measurements of surface‐supported peptides have contributed significantly to the debate. Here we summarize the current approaches to the study of electron transfer in peptides with a focus on surface measurements and comment on these results in light of the current and often controversial debate on electron transfer mechanisms in peptides.
Head‐Group Size or Hydrophilicity of Surfactants: The Major Regulator of Lipase Activity in Cationic Water‐in‐Oil Microemulsions
Authors: Das Debapratim , Roy Sangita , Mitra Rajendra Narayan , Dasgupta Antara , Das Prasanta Kumar 
Published: June 2005

AbstractTo determine the crucial role of surfactant head‐group size in micellar enzymology, the activity of Chromobacterium Viscosum (CV) lipase was estimated in cationic water‐in‐oil (w/o) microemulsions of three different series of surfactants with varied head‐group size and hydrophilicity. The different series were prepared by subsequent replacement of three methyl groups of cetyltrimethylammonium bromide (CTAB) with hydroxyethyl (1–3, series I), methoxyethyl (4–6, series II), and n‐propyl (7–9, series III) groups. The hydrophilicity at the polar head was gradually reduced from series I to series III. Interestingly, the lipase activity was found to be markedly higher for series II surfactants relative to their more hydrophilic analogues in series I. Moreover, the activity remained almost comparable for complementary analogues of both series I and III, though the hydrophilicity was drastically different. Noticeably, the head‐group area per surfactant is almost similar for comparable surfactants of both series I and III, but distinctly higher in case of series II surfactants. Thus the lipase activity was largely regulated by the surfactant head‐group size, which plays the dominant role over the hydrophilicity. The increase in head‐group size presumably allows the enzyme to attain a flexible conformation as well as increase in the local concentration of enzyme and substrate, leading to the higher efficiency of lipase. The lipase showed its best activity in the microemulsion of 6 probably because of its highest head‐group size. Furthermore, the observed activity in 6 is 2–3‐fold and 8‐fold higher than sodium bis(2‐ethyl‐1‐hexyl)sulfosuccinate (AOT) and CTAB‐based microemulsions, respectively, and in fact highest ever in any w/o microemulsions.
Are the Hydrogen Bonds of RNA (A⋅U) Stronger Than those of DNA (A⋅T)? A Quantum Mechanics Study
Authors: Pérez Alberto , Sponer Jiri , Jurecka Petr , Hobza Pavel , Luque F. Javier , Orozco Modesto 
Published: June 2005

AbstractThe intrinsic stability of Watson–Crick d(A⋅T) and r(A⋅U) hydrogen bonds was analyzed by employing a variety of quantum‐mechanical techniques, such as energy calculations, determination of reactivity indexes, and analysis of electron density topology. The analyses were performed not only for equilibrium gas‐phase geometries, but also on hundreds of conformations derived from molecular dynamics (MD) and database analysis. None of our results support the idea that r(A⋅U) hydrogen bonds are intrinsically more stable than those of d(A⋅T). Instead, our data are in accordance with the traditional view that the greater stability of RNA relative to DNA is attributable to a variety of effects (e.g., stacking, sugar puckering, solvation) rather than to a significant difference in the hydrogen bonding of DNA and RNA base pairs.
Site‐Isolated Porphyrin Catalysts in Imprinted Polymers
Authors: Burri Estelle , Öhm Margarita , Daguenet Corinne , Severin Kay 
Published: June 2005

AbstractA meso‐tetraaryl ruthenium porphyrin complex having four polymerizable vinylbenzoxy groups (2) has been synthesized by reaction of pyrrole with 4‐(vinylbenzoxy)benzaldehyde and subsequent metalation with [Ru3(CO)12]. The porphyrin complex was immobilized by copolymerization with ethylene glycol dimethacrylate. The resulting polymer P2 was found to catalyze the oxidation of alcohols and alkanes with 2,6‐dichloropyridine N‐oxide without activation by mineral acids. Under similar conditions, the homogeneous catalyst 2 was completely inefficient. By using diphenylaminomethane and 1‐aminoadamantane as coordinatively bound templates during the polymerization procedure, the molecularly imprinted polymers P3 and P4 have been synthesized. Compared with the polymer P2, the imprinted catalysts displayed a significantly increased activity with rate enhancements of up to a factor of 16.
Equations of Camassa‐Holm type and Jacobi ellipsoidal coordinates
Authors: Vaninsky K. L. 
Published: June 2005

AbstractWe consider the integrable Camassa‐Holm (CH) equation on the line with positive initial data rapidly decaying at infinity. On such a phase space we construct a one‐parameter family of integrable hierarchies that preserves the mixed spectrum of the associated string spectral problem. This family includes the CH hierarchy. We demonstrate that the constructed flows can be interpreted as Hamiltonian flows on the space of Weyl functions of the associated string spectral problem. The corresponding Poisson bracket is the Atiyah‐Hitchin bracket. Using an infinite dimensional version of the Jacobi ellipsoidal coordinates, we obtain a one‐parameter family of canonical coordinates linearizing the flows. © 2005 Wiley Periodicals, Inc.
Study of a highly accurate and fast protein–ligand docking method based on molecular dynamics
Authors: Taufer M. , Crowley M. , Price D. J. , Chien A. A. , Brooks C. L. 
Published: June 2005

AbstractFew methods use molecular dynamics simulations in concert with atomically detailed force fields to perform protein–ligand docking calculations because they are considered too time demanding, despite their accuracy. In this paper we present a docking algorithm based on molecular dynamics which has a highly flexible computational granularity. We compare the accuracy and the time required with well‐known, commonly used docking methods such as AutoDock, DOCK, FlexX, ICM, and GOLD. We show that our algorithm is accurate, fast and, because of its flexibility, applicable even to loosely coupled distributed systems such as desktop Grids for docking. Copyright © 2005 John Wiley & Sons, Ltd.
Parallel protein folding with STAPL
Authors: Thomas Shawna , Tanase Gabriel , Dale Lucia K. , Moreira Jose M. , Rauchwerger Lawrence , Amato Nancy M. 
Published: June 2005

AbstractThe protein‐folding problem is a study of how a protein dynamically folds to its so‐called native state—an energetically stable, three‐dimensional conformation. Understanding this process is of great practical importance since some devastating diseases such as Alzheimer's and bovine spongiform encephalopathy (Mad Cow) are associated with the misfolding of proteins. We have developed a new computational technique for studying protein folding that is based on probabilistic roadmap methods for motion planning. Our technique yields an approximate map of a protein's potential energy landscape that contains thousands of feasible folding pathways. We have validated our method against known experimental results. Other simulation techniques, such as molecular dynamics or Monte Carlo methods, require many orders of magnitude more time to produce a single, partial trajectory. In this paper we report on our experiences parallelizing our method using STAPL (Standard Template Adaptive Parallel Library) that is being developed in the Parasol Lab at Texas A&M. An efficient parallel version will enable us to study larger proteins with increased accuracy. We demonstrate how STAPL enables portable efficiency across multiple platforms, ranging from small Linux clusters to massively parallel machines such as IBM's BlueGene/L, without user code modification. Copyright © 2005 John Wiley & Sons, Ltd.
Dynamic programming for LR‐PCR segmentation of bacterium genomes
Authors: Andonov Rumen , Lavenier Dominique , Veber Philippe , Yanev Nicola 
Published: June 2005

AbstractBacterium genome plasticity can efficiently be studied by the long‐range polymerase chain reaction (LR‐PCR) technique: genomes of different strains are split into hundreds of short segments which, after LR‐PCR amplification, are used to sketch profiles. The segments have to: (1) cover the entire genome; (2) overlap each other; and (3) be of nearly identical size. This paper addresses the problem of finding a list of segments satisfying these constraints ‘as much as possible’. Two algorithms based on dynamic programming approach are presented. They differ on the optimization criteria for measuring the quality of the covering. The first considers the maximal deviation of the segment lengths relatively to an ideal length. The second automatically finds a segment length that minimizes the maximal deviation. Copyright © 2005 John Wiley & Sons, Ltd.
Parallel RNA secondary structure prediction using stochastic context‐free grammars
Authors: Liu Tong , Schmidt Bertil 
Published: June 2005

AbstractWith the growing number of known RNA genes efficient and accurate computational analysis of RNA sequences is becoming increasingly important. Stochastic context‐free grammars (SCFGs) are used as a popular tool to model RNA secondary structures. However, algorithms for aligning a RNA sequence to a SCFG are highly compute‐intensive. This has so far limited applications of SCFGs to relatively small problem sizes. In this paper we present the design of a parallel RNA sequence‐structure alignment algorithm. Its implementation on parallel systems leads to significant runtime savings. This makes it possible to compute sequence‐structure alignments of even the largest RNAs such as small subunit ribosomal rRNAs and long subunit ribosomal rRNAs in reasonable time. Copyright © 2005 John Wiley & Sons, Ltd.
Peptide identification via constrained multi‐objective optimization: Pareto‐based genetic algorithms
Authors: Malard J. M. , Heredia‐Langner A. , Cannon W. R. , Mooney R. , Baxter D. J. 
Published: June 2005

AbstractAutomatic peptide identification from collision‐induced dissociation tandem mass spectrometry data using optimization techniques is made difficult by large plateaus in the fitness landscapes of scoring functions, by the fuzzy nature of constraints from noisy data and by the existence of diverse but equally justifiable probabilistic models of peak matching. Here, two different scoring functions are combined into a parallel multi‐objective optimization framework. It is shown how multi‐objective optimization can be used to empirically test for independence between distinct scoring functions. The loss of selection pressure during the evolution of a population of putative peptide sequences by a Pareto‐driven genetic algorithm is addressed by alternating between two definitions of fitness according to a numerical threshold. Copyright © 2005 John Wiley & Sons, Ltd.
RAxML‐II: a program for sequential, parallel and distributed inference of large phylogenetic trees
Authors: Stamatakis Alexandros , Ludwig Thomas , Meier Harald 
Published: June 2005

AbstractInference of phylogenetic trees comprising hundreds or even thousands of organisms based on the maximum likelihood method is computationally intensive. We present simple heuristics which yield accurate trees for synthetic as well as real data and significantly reduce execution time. Those heuristics have been implemented in a sequential, parallel, and distributed program called RAxML‐II, which is freely available as open source code. We compare the performance of the sequential program with PHYML and MrBayes which—to the best of our knowledge—are currently the fastest and most accurate programs for phylogenetic tree inference based on statistical methods. Experiments are conducted using 50 synthetic 100 taxon alignments as well as nine real‐world alignments comprising 101 up to 1000 sequences. RAxML‐II outperforms MrBayes for real‐world data both in terms of speed and final likelihood values. Furthermore, for real data RAxML‐II requires less time (a factor of 2–8) than PHYML to reach PHYML's final likelihood values and yields better final trees due to its more exhaustive search strategy. For synthetic data MrBayes is slightly more accurate than RAxML‐II and PHYML but significantly slower. The non‐deterministic parallel program shows good speedup values and has been used to infer a 10 000‐taxon tree comprising organisms from the domains Eukarya, Bacteria, and Archaea. Copyright © 2005 John Wiley & Sons, Ltd.