Home About us Contact
|
Home About us Contact | ||
|
|
||
Mechanistic Aspects (mechanistic + aspect)
Selected AbstractsSignificant Self-Acceleration Effects of Nitrile Additives in the Rhodium-Catalyzed Conversion of Aldoximes to Amides: A New Mechanistic AspectADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2009Min Kim Abstract It was found that the catalytic activity of rhodium complexes was highly sensitive to the type of N-heterocyclic carbene (NHC) ligands in the conversion of aldoximes to amides. Among those species examined, the (cyclooctadiene)rhodium chloride-carbene complex Rh(cod)(IMes)Cl exhibited the highest reactivity when it was employed in combination with a Brønsted acid, thus allowing mild reaction conditions. A significant rate acceleration effect resulting from the addition of nitrile additives was also observed. With the new protocol, the substrate scope of aldoximes has been widely expanded to include sterically congested and electronically varied derivatives. On the basis of detailed mechanistic studies, it is proposed that the reaction proceeds mainly via intramolecular electrophilic addition of aldoxime to rhodium-bound nitrile, which is different from the generally postulated two-step route: dehydration of aldoxime to nitrile followed by hydration of the latter intermediate. [source] Synthetic and Mechanistic Aspects of Acid-Catalyzed Disproportionation of Dialkyl Diarylmethyl Ethers: A Combined Experimental and Theoretical StudyEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 25 2009Margherita Barbero Abstract The disproportionation reactions of various dialkyl diarylmethyl ethers have been carried out in the presence of a catalytic amount (10 mol-%) of o -benzenedisulfonimide as a Brønsted acid catalyst; the reaction conditions were mild, and the yields of the diarylmethane target products were good. The catalyst was easily recovered and purified, ready to be used in further reactions. The theoretical study confirmed that the reaction proceeds in two steps: The formation of a carbocation from the protonated ether followed by hydride transfer. Although the hydride transfer is the rate-determining step, it is the stability of the carbocation that determines the reaction rate and therefore the yields. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Microwave-Assisted Dimroth Rearrangement of Thiazines to Dihydropyrimidinethiones: Synthetic and Mechanistic AspectsMOLECULAR INFORMATICS, Issue 5-6 2006Abstract The Dimroth rearrangement of a set of substituted 2-amino-6H -1,3-thiazines into 3,4-dihydropyrimidine-2-thiones was investigated. The rearrangements were carried out under microwave irradiation conditions in batch or continuous flow format, employing either toluene or 1-methyl-2-pyrrolidone as solvent. Thiazines bearing an ester group at the C5 position rearranged at a considerably higher temperature than derivatives without substituents at this position into the corresponding pyrimidinethiones. This strictly thermal rearrangement was studied in detail using differential scanning calorimetry and density functional theory computational methods. The reaction pathway involves a zwitterionic intermediate. [source] ChemInform Abstract: A Highly Chemoselective Oxidation of Alcohols to Carbonyl Products with Iodosobenzene Diacetate Mediated by Chromium(III)(salen) Complexes: Synthetic and Mechanistic Aspects.CHEMINFORM, Issue 2 2001Waldemar Adam Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Glycerol Etherification over Highly Active CaO-Based Materials: New Mechanistic Aspects and Related Colloidal Particle FormationCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2008Agnieszka Abstract Glycerol is an attractive renewable building block for the synthesis of di- and triglycerols, which have numerous applications in the cosmetic and pharmaceutical industries. In this work, the selective etherification of glycerol to di- and triglycerol was studied in the presence of alkaline earth metal oxides and the data are compared with those obtained with Na2CO3 as a homogeneous catalyst. It was found that glycerol conversion increased with increasing catalyst basicity; that is, the conversion increases in the order: MgO Flavonoids as RTK inhibitors and potential anticancer agentsMEDICINAL RESEARCH REVIEWS, Issue 5 2008Florence Teillet Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715,745, 2008 [source] Studies on the mechanism of rapid activation of protein tyrosine phosphorylation activities, particularly c-Src kinase, by TCDD in MCF10AJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2005Olga Mazina Abstract While the process of the Ah receptor activation leading to cytochrome P450 induction has been well studied, the mechanism and the process through which the Ah receptor activates tyrosine kinases, within a few minutes of its ligand binding, is not known. Previously, it was reported by Tannheimer et al. (Carcinogenesis 1998; 19:1291,1297) that TCDD causes rapid induction of tyrosine phosphorylation activities in the MCF10A human mammary epithelial cell line. To study the mechanistic aspect of this phenomenon, particularly that occurs within a few minutes after administration, we first studied the effect of insulin on MCF10A under serum free conditions with added EGF. The addition of insulin induced a rapid (5 min) tyrosine phosphorylation on several 160,190 kDa proteins which was followed by significant dephosphorylation activities on these proteins by 15 min. TCDD increased the rate of tyrosine phosphorylation on those proteins but at 15 min, the level of phosphorylation was still high. When insulin and TCDD were added together, the ability of insulin to induce de-phosphorylation by 15 min disappeared. Such an action of TCDD was accompanied by an increase in the titer of the activated form of Src kinase (i.e. c-Src protein with 418 tyrosine phosphorylation), and a concomitant decrease in the level of 529 tyrosine phosphorylated form (an inactivated form). The TCDD-induced activation of c-Src could be blocked by pretreated MCF10A cells with antisense oligonucleotides against c-src or with a specific inhibitor of Src kinase, PP-2. These results support the conclusion that c-Src kinase is at least one of the earliest and the most upstream components of toxic signaling of the Ah-receptor activated by TCDD through the post-transcriptional process. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:313,321, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20041 [source] Non-apoptotic cell death in Caenorhabditis elegansDEVELOPMENTAL DYNAMICS, Issue 5 2010Manolis Vlachos Abstract The simple nematode worm Caenorhabditis elegans has been instrumental in deciphering the molecular mechanisms underlying apoptosis. Beyond apoptosis, several paradigms of non-apoptotic cell death, either genetically or extrinsically triggered, have also been described in C. elegans. Remarkably, non-apoptotic cell death in worms and pathological cell death in humans share numerous key features and mechanistic aspects. Such commonalities suggest that similarly to apoptosis, non-apoptotic cell death mechanisms are also conserved, and render the worm a useful organism, in which to model and dissect human pathologies. Indeed, the genetic malleability and the sophisticated molecular tools available for C. elegans have contributed decisively to advance our understanding of non-apoptotic cell death. Here, we review the literature on the various types of non-apoptotic cell death in C. elegans and discuss the implications, relevant to pathological conditions in humans. Developmental Dynamics 239:1337,1351, 2010. © 2010 Wiley-Liss, Inc. [source] Methanol exposure interferes with morphological cell movements in the Drosophila embryo and causes increased apoptosis in the CNSDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2004Dervla M. Mellerick Abstract Despite the significant contributions of tissue culture and bacterial models to toxicology, whole animal models for developmental neurotoxins are limited in availability and ease of experimentation. Because Drosophila is a well understood model for embryonic development that is highly accessible, we asked whether it could be used to study methanol developmental neurotoxicity. In the presence of 4% methanol, approximately 35% of embryos die and methanol exposure leads to severe CNS defects in about half those embryos, where the longitudinal connectives are dorsally displaced and commissure formation is severely reduced. In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure. Although we did not find any evidence to suggest that methanol exposure affects the capacity of neuroblasts to divide or induces inappropriate apoptosis in these cells, in the CNS of germ band retracted embryos, the number of apoptotic nuclei is significantly increased in methanol-exposed embryos in comparison to controls, particularly in and adjacent to the ventral midline. Apoptosis contributes significantly to methanol neurotoxicity because embryos lacking the cell death genes grim, hid, and reaper have milder CNS defects resulting from methanol exposure than wild-type embryos. Our data suggest that when neurons and glia are severely adversely affected by methanol exposure, the damaged cells are cleared by apoptosis, leading to embryonic death. Thus, the Drosophila embryo may prove useful in identifying and unraveling mechanistic aspects of developmental neurotoxicity, specifically in relation to methanol toxicity. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 308,318, 2004 [source] Landscape approaches to stream fish ecology, mechanistic aspects of habitat selection and behavioral ecology.ECOLOGY OF FRESHWATER FISH, Issue 1-2 2000Introduction, commentary No abstract is available for this article. [source] Recent developments in peptide stereoisomer separations by capillary electromigration techniquesELECTROPHORESIS, Issue S1 2009Gerhard K. E. Scriba Abstract The stereochemistry of peptides determines their physicochemical and biological activities. Thus, analytical methods that are able to discriminate between peptide stereoisomers are important. As peptides are typically hydrophilic compounds, many methods for the separation of peptide diastereomers and enantiomers have been developed by capillary electromigration techniques. Moreover, peptide enantiomers displayed unique migration behavior such as a pH-dependent change of the enantiomer migration order in CD-mediated enantioseparations in CE making them ideal compounds to study mechanistic effects of enantioseparations. The present short review summarizes recent developments in the separation of stereoisomers of peptide and peptidomimetics by capillary electromigration techniques. Moreover, recent NMR and molecular modeling studies as well as investigation on the effect of buffer additives on complex formation will be discussed as attempts to understand mechanistic aspects of peptide enantioseparations and to analyze the structure of peptide-CD complexes. [source] Recent advances in enantioseparations of peptides by capillary electrophoresisELECTROPHORESIS, Issue 22-23 2003Gerhard K. E. Scriba Abstract The present review summarizes peptide enantioseparations by capillary electrophoresis with the focus on recent developments. These include the application of new chiral selectors and systematic studies involving series of di- and tripeptides with either common features or with a variety of structures. One section emphasizes mechanistic aspects of the migration order of the enantiomers in cyclodextrin-assisted chiral separations with respect to the complexation constants and the mobilities of the transient diastereomeric complexes. In addition, short paragraphs on the application of chiral capillary electrophoresis to the determination of the stereochemical purity of peptidomimetics and on chiral separations of peptides by capillary electrochromatography have also been included. [source] Ruthenium-Catalyzed Allenyl Carbamate Formation from Propargyl Alcohols and IsocyanatesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2008Edgar Haak Abstract Ruthenium complexes of redox-coupled cyclopentadienone ligands catalyze the formation of allenyl carbamates from propargyl alcohols and isocyanates. This efficient and atom-economical process represents the first catalytic access to allenyl carbamates, compounds of high synthetic potential. The reaction needs an acidic co-catalyst and can be performed at room temperature. In addition, new (cyclopentadienone)iron and -ruthenium complexes were synthesized, and mechanistic aspects regarding catalytic transformations of propargyl systems with ruthenium catalysts are obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Ligand Effects on the Mechanisms of Thermal Bond Activation in the Gas-Phase Reactions NiX+/CH4,Ni(CH3)+/HX (X=H, CH3, OH, F).HELVETICA CHIMICA ACTA, Issue 12 2008Short Communication Abstract The thermal ion-molecule reactions NiX++CH4,Ni(CH3)++HX (X=H, CH3, OH, F) have been studied by mass spectrometric methods, and the experimental data are complemented by density functional theory (DFT)-based computations. With regard to mechanistic aspects, a rather coherent picture emerges such that, for none of the systems studied, oxidative addition/reductive elimination pathways are involved. Rather, the energetically most favored variant corresponds to a , -complex-assisted metathesis (, -CAM). For X=H and CH3, the ligand exchange follows a ,two-state reactivity (TSR)' scenario such that, in the course of the thermal reaction, a twofold spin inversion, i.e., triplet,singlet,triplet, is involved. This TSR feature bypasses the energetically high-lying transition state of the adiabatic ground-state triplet surface. In contrast, for X=F, the exothermic ligand exchange proceeds adiabatically on the triplet ground state, and some arguments are proposed to account for the different behavior of NiX+/Ni(CH3)+ (X=H, CH3) vs. NiF+. While the couple Ni(OH)+/CH4 does not undergo a thermal ligand switch, the DFT computations suggest a potential-energy surface that is mechanistically comparable to the NiF+/CH4 system. Obviously, the ligands X act as a mechanistic distributor to switch between single vs. two-state reactivity patterns. [source] Synthetic and mechanistic aspects of preparation of phosphinito- and phosphito-mercuries,HETEROATOM CHEMISTRY, Issue 3 2008Jacek E. Nycz A >PO, (1) type of anion has been used as an efficient synthetic precursor of four-coordinated compounds: R2P(O)Hg(O)PR2 (5) and R2P(O)HgBz (3) (R = alkoxy, alkyl, aryl). They were obtained in good yield. Bis(t -butyl-phenylphosphinito-P)mercury (meso and rac) (5c,d) selectively decomposed into 1,2-di- t -butyl-1,2-diphenyldiphosphane 1,2-dioxide (meso and rac) (6c,d). Furthermore, some mechanistic aspects of the synthesis of mentioned compounds are elaborated.© 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:234,237, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20409 [source] Metal-complex formation and DNA interaction of 5, 10,15,20-tetrakis(1-methyl-4-pyridiyl)-porphine: Study of the mechanistic aspectsINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 2 2010Sabriye Aydinoglu The macrocyclic porphyrin 5,10,15,20-tetrakis(1-methyl-4-pyridiyl)-porphine is studied in its ability to coordinate Cu(II) even at very low pH values and to interact, as a copper complex, with calf-thymus (CT-DNA). The kinetics and equilibria for metal-ligand complexes formation are spectrophotometrically studied, particularly focussing on the mechanistic information provided by the kinetic approach. The rate constants of complex formation is much lower than that of water exchange at Cu(II); this behavior is ascribed to an equilibrium between two porphyrin populations, only one of them being reactive. Concerning the interaction of the copper,porphyrin complex (D) with CT-DNA, it has been found that the complex binds to G,C base pairs by intercalation while forms external complex with the A,T base pairs. The kinetic results agree with a reaction mechanism that takes into account the slow shuffling from an AT-bound form (DAT) to a GC-bound form (DGC) of the copper complex (D), finally leading to a more stable DGC* intercalated form. Kinetic and equilibrium parameters for the copper complex binding to the nucleic acid are obtained, and the binding mechanism is discussed. A mechanism is proposed where D reacts simultaneously with (G,C) and (A,T) base pairs. The resulting bound forms interconvert according to a "shuffling" process, which involves formation of an intermediate (DGC) form. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 42: 79,89, 2010 [source] Methoxycarbonylation of Aliphatic Diamines with Dimethyl Carbonate Promoted by in situ Generated Hydroxide Ion: A Mechanistic ConsiderationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Dae Won Kim Abstract The methoxycarbonylation reactions of aliphatic diamines with dimethyl carbonate are accelerated greatly in the presence of water. Theoretical investigations on the mechanistic aspects of the methoxycarbonylation of 1,6-hexanediamine strongly suggest that the hydroxide ion, generated in situ from the interaction of 1,6-hexanediamine with water, is an active catalytic species and plays a pivotal role in the rate-determining hydrogen abstraction step from the amino group. [source] Preparation of Arylphosphonates by Palladium(0)-Catalyzed Cross-Coupling in the Presence of Acetate Additives: Synthetic and Mechanistic StudiesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 18 2009Marcin Kalek Abstract An efficient protocol for the synthesis of arylphosphonate diesters via a palladium-catalyzed cross-coupling of H-phosphonate diesters with aryl electrophiles, promoted by acetate ions, was developed. A significant shortening of the cross-coupling time in the presence of the added acetate ions was achieved for bidentate and monodentate supporting ligands, and for different aryl electrophiles (iodo, bromo and triflate derivatives). The reaction conditions were optimized in terms of amount of the catalyst, supporting ligands, and source of the acetate ion used. Various arylphosphonates, including those of potential biological significance, were synthesized using this newly developed protocol. Some mechanistic aspects of the investigated reactions are also discussed. [source] Transcriptional activities of mutant p53: When mutations are more than a lossJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Ella Kim Abstract The dominant oncogenic properties of mutant p53 have been recognized as a phenomenon associated with tumor progression a long time ago, even before it was realized that the major function of wild type p53 is that of a tumor suppressor. Recent advances in this fascinating area in tumor cell biology reveal that the community of mutant p53 proteins is comprised of proteins that are extremely diverse both structurally and functionally, and elicit a multitude of cellular responses that not only are entirely distinct from those mediated by wild type p53, but also vary among different mutant p53 proteins. Aberrant regulation of transcription is one of the mechanisms underlying the ability of some mutant p53 proteins to act as oncogenic factors. Systematic analyses of the transcriptional activities of mutant p53 suggest that not the loss of transcriptional activity as such, but alterations of target DNA selectivity may be the driving force of mutant p53 specific transcription underlying the growth-promoting effects of mutant p53. This article focuses on mechanistic aspects of mutp53 "gain-of-function" with the emphasis on possible mechanisms underlying transcriptional activation by mutp53. © 2004 Wiley-Liss, Inc. [source] Solid-solid reactions in series: A modeling and experimental studyAICHE JOURNAL, Issue 9 2009A. K. Suresh Abstract Reactions among particulate solid phases are important and abundant in many materials, chemical, and metallurgical process industries. Many of these are reaction networks, and not single-step reactions as normally assumed. There is no theoretical framework available for the analysis of such systems, and single-reaction models derived from the gas,solid literature continue to be used. Formation of cement clinker in the rotary cement kiln is a prime example of the genre, in which mechanistic aspects play an important role in determining energy efficiency and the composition and nature of the phases that form. In the present study, we formulate a model within the ambit of the "shrinking core" class of models, for reactions in series among solid phases. The model shows the presence of one or two moving fronts in the reacting particle, depending on the relative rates of the processes involved. A single Thiele-type parameter controls the model behavior, at once describing the relative rates of the intermediate formation and consumption processes, and the diffusion-reaction competition for the product formation step. The model has been shown to reduce to the well known single reaction models at the limits of low and high values of the Thiele parameter. Experimental data have been obtained on the calcia-alumina system, an important one in cement manufacture, in the temperature range 1150,1250°C. The model has been fitted to these data and the kinetic parameters determined. The comparison bears out the salient features of the theory, and shows that a degree of diffusion limitation exists for the intermediate conversion step under these conditions. The diffusivity values estimated are in the range of 10,19 to 10,18 m2/s and agree with values found in the literature for similar systems. The rate constant for the intermediate conversion step is of the order of 10,6 s,1. This being among the first such determinations, this value awaits confirmation from other studies. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Ionic liquids: solvent properties and organic reactivityJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2005Cinzia Chiappe Abstract Ionic liquids are a fascinating class of novel solvents, which are attracting attention as possible ,green' alternative to volatile molecular organic solvents to be applied in catalytic and organic reactions and electrochemical and separation processes. Over 200 room temperature ionic liquids are known but for most of them physico-chemical data are incomplete or lacking. Furthermore, despite the incredible number of potential ionic liquids (evaluated as ,>,1014), generally only a few imidazolium-based salts are used in synthesis. Moreover, most of the data reported to date were focused on the effect that these new solvents have on chemical reaction products; only a few reports evidence the effect on reaction mechanisms or rate or equilibrium constants. In this review, the physico-chemical properties of the most used ionic liquids, that are relevant to synthesis, are discussed and a decided emphasis is placed on those properties that most clearly illuminate the ability of ionic liquids to affect the mechanistic aspects of some organic reactions. Copyright © 2004 John Wiley & Sons, Ltd. [source] Relationship between nucleophilicity/electrophilicity indices and reaction mechanisms for the nucleophilic substitution reactions of carbonyl compoundsJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2004Paola Campodonico Abstract Theoretical electrophilicity and nucleophilicity scales, defined in terms of electronic reactivity indices, were tested for the reaction of a series of carbonates with neutral and charged reagents of varying nucleophilicity. The electrophilicity and nucleophilicity scales were used to rationalize some mechanistic aspects developed by these reacting systems: the greater the electrophilicity/nucleophilicity difference, the more concerted the reaction mechanism will be. Conversely, a small electrophilicity/nucleophilicty gap will in general be associated with a stepwise reaction mechanism. Copyright © 2004 John Wiley & Sons, Ltd. [source] Liquid-Glassy Polymer Diffusion: Effects of Liquid Molecular Weight and TemperatureMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 10 2007J. Pablo Tomba Abstract We examine mechanistic aspects of the diffusion between a series of liquid polystyrenes (PS) and a glassy poly(phenylene oxide) (PPO) matrix, through the use of confocal Raman microspectroscopy. The results show that the diffusion kinetics has Fickean characteristics, similar to those found in liquid-liquid polymer diffusion. No signatures of the linear regime typical of the case-II diffusion mechanism were found. Overall, these observations are consistent with the claim that case-II is unlikely to occur in liquid-glassy polymer diffusion. [source] Nonsteroidal aromatase inhibitors: Recent advancesMEDICINAL RESEARCH REVIEWS, Issue 3 2002Maurizio Recanatini Abstract Aromatase is the cytochrome P450 enzyme responsible for the last step of estrogen biosynthesis, and aromatase inhibitors constitute an important class of drugs in clinical use for the treatment of breast cancer. Nonsteroidal aromatase inhibitors (NSAIs) are competitive inhibitors of aromatase, which bind to the enzyme active site by coordinating the iron atom present in the heme group of the P450 protein. Presently, third generation NSAIs are in use, and research efforts are being carried out both to identify new molecules of therapeutic interest and to clarify the mechanism of action. In this article, we present a survey of the compounds that have been recently reported as NSAIs, to provide a broad view on the general structure,activity relationships of the class. Moreover, starting from the current knowledge of the mechanistic aspects of aromatase action and from recent theoretical work on the molecular modeling of both enzyme and inhibitors, we try to indicate a way to integrate these different studies in view of a more general understanding of the aromeatase-inhibitor system. Finally, some aspects regarding the possible future development of the field are considered briefly. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 3, 282,304, 2002; Published online in wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10010 [source] Topological analysis of Hin-catalysed DNA recombination in vivo and in vitroMOLECULAR MICROBIOLOGY, Issue 4 2004Stacy K. Merickel Summary In vitro studies have demonstrated that Hin-catalysed site-specific DNA inversion occurs within a tripartite invertasome complex assembled at a branch on a supercoiled DNA molecule. Multiple DNA exchanges within a recombination complex (processive recombination) have been found to occur with particular substrates or reaction conditions. To investigate the mechanistic properties of the Hin recombination reaction in vivo , we have analysed the topology of recombination products generated by Hin catalysis in growing cells. Recombination between wild-type recombination sites in vivo is primarily limited to one exchange. However, processive recombination leading to knotted DNA products is efficient on substrates containing recombination sites with non-identical core nucleotides. Multiple exchanges are limited by a short DNA segment between the Fis-bound enhancer and closest recombination site and by the strength of Fis,Hin interactions, implying that the enhancer normally remains associated with the recombining complex throughout a single exchange reaction, but that release of the enhancer leads to multiple exchanges. This work confirms salient mechanistic aspects of the reaction in vivo and provides strong evidence for the propensity of plectonemically branched DNA in prokaryotic cells. We also demonstrated that a single DNA exchange resulting in inversion in vitro is accompanied by a loss of four negative supercoils. [source] Epidemic of plurality and contributions of assisted reproductive technology therein,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2009Monica Kapoor Abstract A commentary on contributions of ART to the pandemic of multiple gestations is presented and mechanistic aspects therein are explored. © 2009 Wiley-Liss, Inc. [source] Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutationsPROTEIN SCIENCE, Issue 10 2002Stefano Piana Abstract The emergence of drug-resistant variants is a serious side effect associated with acquired immune deficiency syndrome therapies based on inhibition of human immunodeficiency virus type 1 protease (HIV-1 PR). In these variants, compensatory mutations, usually located far from the active site, are able to affect the enzymatic activity via molecular mechanisms that have been related to differences in the conformational flexibility, although the detailed mechanistic aspects have not been clarified so far. Here, we perform multinanosecond molecular dynamics simulations on L63P HIV-1 PR, corresponding to the wild type, and one of its most frequently occurring compensatory mutations, M46I, complexed with the substrate and an enzymatic intermediate. The quality of the calculations is established by comparison with the available nuclear magnetic resonance data. Our calculations indicate that the dynamical fluctuations of the mutated enzyme differ from those in the wild type. These differences in the dynamic properties of the adducts with the substrate and with the gem-diol intermediate might be directly related to variations in the enzymatic activity and therefore offer an explanation of the observed changes in catalytic rate between wild type and mutated enzyme. We anticipate that this "flexibility-assisted" mechanism might be effective in the vast majority of compensatory mutations, which do not change the electrostatic properties of the enzyme. [source] Crystallization and preliminary crystallographic analysis of the global nitrogen regulator AmtR from Corynebacterium glutamicumACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2009Kristin Hasselt AmtR, a member of the TetR family of transcription regulators, is a global regulator of nitrogen control in Corynebacterium glutamicum. Unlike other TetR-family members, which are regulated by small-molecule effectors, AmtR is regulated by a protein called GlnK. It has been shown that a GlnK trimer has to become adenylylated prior to formation of a complex with AmtR. The physiological function of AmtR has been very well studied, but structural characterization of the mechanistic aspects of AmtR-regulated transcription has yet to be accomplished. AmtR has successfully been crystallized in space group P21212, with six molecules in the asymmetric unit and unit-cell parameters a = 153.34, b = 163.10, c = 51.93,Å. Preliminary phases were obtained using Se-SAD. [source] Telomere dynamics: the means to an endCELL PROLIFERATION, Issue 4 2007M. Matuli Creating the physical ends of linear chromosomes, they play a crucial role in maintaining genome stability, control of cell division, cell growth and senescence. In vertebrates, telomeres consist of G-rich repetitive DNA sequences (TTAGGG)n and specific proteins, creating a specialized structure called the telosome that through mutual interactions with many other factors in the cell give rise to dynamic regulation of chromosome maintenance. In this review, we survey the structural and mechanistic aspects of telomere length regulation and how these processes lead to alterations in normal and immortal cell growth. [source] Competitive Hydrogen-Atom Abstraction versus Oxygen-Atom and Electron Transfers in Gas-Phase Reactions of [X4O10].+ (X=P, V) with C2H4CHEMISTRY - A EUROPEAN JOURNAL, Issue 15 2010Nicolas Dietl Dipl.-Chem. Why so different? The comparison of the reaction of "bare" [P4O10].+ and [V4O10].+ with ethene by mass-spectrometric and computational studies permits insight into mechanistic aspects of the competition between CH bond activation and oxygen-atom and electron transfers. Whereas [P4O10].+ reacts by homolytic CH bond cleavage and electron transfer, the isostructural [V4O10].+ shows only oxygen-atom transfer (see picture). [source]
| | |||||||||||||||||||||||||||