Search for Millimeter Microwave Effects on Enzyme or Protein Functions

1979 ◽  
Vol 34 (1-2) ◽  
pp. 60-63 ◽  
Author(s):  
P. Tuengler ◽  
F. Keilmann ◽  
L. Genzel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Microwave Irradiation ◽  
Reaction Rate ◽  
Cooperative Binding ◽  
Irradiation Intensity ◽  
Biological Responses ◽  
Protein Functions ◽  
Microwave Effects

Abstract Recent observations of nonthermal, resonant biological responses to weak millimeter microwave irradiation have led us to investigate whether similar influences exist on enzymatic functions in vitro. We chose (i) the reduction of ethanol in the presence of alcohol dehydrogenase and (ii) the cooperative binding of oxygen on hemoglobin. Using an irradiation intensity near 10 mW/cm2 the frequency was continuously varied from 40 to 115 GHz with a resolution of a few MHz. No micro­ wave influences were detectable within our experimental sensitivity of about 0.1% of the reaction rate in (i), or of the amount of bound oxygen at half saturation in (ii).

scholarly journals Preliminary observations on the copolymerisation of acceptor monomer:donor monomer systems under microwave irradiation

2005 ◽  
Vol 3 (1) ◽  
pp. 40-52 ◽  
Author(s):  
Christopher Fellows
Keyword(s):  
Molecular Weight ◽  
Free Radical ◽  
Microwave Irradiation ◽  
Chemical Reactions ◽  
Reaction Rate ◽  
Rate Enhancement ◽  
Radical Recombination ◽  
Donor Acceptor ◽  
Microwave Effects

AbstractThe mechanistic rationalisation of specific ‘microwave effects’ previously reported in a range of chemical reactions suggests that they may be observable in the freeradical copolymerisation of comonomer pairs capable of forming donor-acceptor complexes. Polymerisation under microwave irradiation is carried out for several comonomer pairs with weak donor-acceptor interactions, and no acceleration in rate or change in degree of alternation attributable to changes in propagation are observed. An increase in reaction rate of 150–200 % is observed for all systems, with trends in molecular weight suggesting this was due to an increase in radical flux. This is consistent with earlier reports of rate enhancement for free-radical polymerisations using the initiator 2,2′-azobis-isobutyronitrile, and it is proposed that microwave irradiation may reduce the amount of geminate radical recombination.

Uncertainties Associated with Assessing the Risk of an Endocrine Active Substance in the Canadian Environment

2001 ◽  
Vol 36 (2) ◽  
pp. 319-330 ◽  
Author(s):  
Mark Servos ◽  
Don Bennie ◽  
Kent Burnison ◽  
Philippa Cureton ◽  
Nicol Davidson ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Endocrine Disruption ◽  
Endocrine System ◽  
Problem Formulation ◽  
Normal Function ◽  
Weight Of Evidence ◽  
Biological Responses ◽  
Low Concentrations ◽  
Multigenerational Effects

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.

Approach in improving potency and selectivity of kinase inhibitors: Allosteric kinase inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Shangfei Wei ◽  
Tianming Zhao ◽  
Jie Wang ◽  
Xin Zhai
Keyword(s):  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Binding Modes ◽  
Allosteric Inhibitors ◽  
Wide Range ◽  
Allosteric Sites ◽  
Protein Functions ◽  
Regulate Protein

: Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structureactivity relationships, ligand-protein interactions and in vitro and in vivo activity. Additionally, challenges as well as opportunities are presented.

scholarly journals EANM position paper on the role of radiobiology in nuclear medicine

2021 ◽  
Author(s):  
An Aerts ◽  
Uta Eberlein ◽  
Sören Holm ◽  
Roland Hustinx ◽  
Mark Konijnenberg ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Absorbed Dose ◽  
Added Value ◽  
External Irradiation ◽  
Executive Summary ◽  
Dose Rates ◽  
Biological Responses ◽  
Medical Physicists ◽  
Radiation Induced

Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

scholarly journals Acceleration of cellodextrin phosphorolysis for bioelectricity generation from cellulosic biomass by integrating a synthetic two-enzyme complex into an in vitro synthetic enzymatic biosystem

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongdong Meng ◽  
Ranran Wu ◽  
Juan Wang ◽  
Zhiguang Zhu ◽  
Chun You
Keyword(s):  
Reaction Rate ◽  
Specific Interaction ◽  
Renewable Resource ◽  
Cellulosic Biomass ◽  
Initial Reaction ◽  
Enzyme Complex ◽  
Bioelectricity Generation ◽  
Favorable Reaction ◽  
Enzyme Complexes

Abstract Background Cellulosic biomass, the earth’s most abundant renewable resource, can be used as substrates for biomanufacturing biofuels or biochemicals via in vitro synthetic enzymatic biosystems in which the first step is the enzymatic phosphorolysis of cellodextrin to glucose 1-phosphate (G1P) by cellodextrin phosphorylase (CDP). However, almost all the CDPs prefer cellodextrin synthesis to phosphorolysis, resulting in the low reaction rate of cellodextrin phosphorolysis for biomanufacturing. Results To increase the reaction rate of cellodextrin phosphorolysis, synthetic enzyme complexes containing CDP and phosphoglucomutase (PGM) were constructed to convert G1P to glucose 6-phosphate (G6P) rapidly, which is an important intermediate for biomanufacturing. Four self-assembled synthetic enzyme complexes were constructed with different spatial organizations based on the high-affinity and high-specific interaction between cohesins and dockerins from natural cellulosomes. Thus, the CDP–PGM enzyme complex with the highest enhancement of initial reaction rate was integrated into an in vitro synthetic enzymatic biosystem for generating bioelectricity from cellodextrin. The in vitro biosystem containing the best CDP–PGM enzyme complex exhibited a much higher current density (3.35-fold) and power density (2.14-fold) than its counterpart biosystem containing free CDP and PGM mixture. Conclusions Hereby, we first reported bioelectricity generation from cellulosic biomass via in vitro synthetic enzymatic biosystems. This work provided a strategy of how to link non-energetically favorable reaction (cellodextrin phosphorolysis) and energetically favorable reaction (G1P to G6P) together to circumvent unfavorable reaction equilibrium and shed light on improving the reaction efficiency of in vitro synthetic enzymatic biosystems through the construction of synthetic enzyme complexes.

scholarly journals Tobacco Mosaic Virus Movement Protein Functions as a Structural Microtubule-Associated Protein

2006 ◽  
Vol 80 (17) ◽  
pp. 8329-8344 ◽  
Author(s):  
Jamie Ashby ◽  
Emmanuel Boutant ◽  
Mark Seemanpillai ◽  
Adrian Sambade ◽  
Christophe Ritzenthaler ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Movement Protein ◽  
Cell Extract ◽  
Transport Processes ◽  
In Vitro Assays ◽  
Protein Functions ◽  
Intercellular Spread

ABSTRACT The cell-to-cell spread of Tobacco mosaic virus infection depends on virus-encoded movement protein (MP), which is believed to form a ribonucleoprotein complex with viral RNA (vRNA) and to participate in the intercellular spread of infectious particles through plasmodesmata. Previous studies in our laboratory have provided evidence that the vRNA movement process is correlated with the ability of the MP to interact with microtubules, although the exact role of this interaction during infection is not known. Here, we have used a variety of in vivo and in vitro assays to determine that the MP functions as a genuine microtubule-associated protein that binds microtubules directly and modulates microtubule stability. We demonstrate that, unlike MP in whole-cell extract, microtubule-associated MP is not ubiquitinated, which strongly argues against the hypothesis that microtubules target the MP for degradation. In addition, we found that MP interferes with kinesin motor activity in vitro, suggesting that microtubule-associated MP may interfere with kinesin-driven transport processes during infection.

scholarly journals Catalytic and Molecular Properties of the Quinohemoprotein Tetrahydrofurfuryl Alcohol Dehydrogenase from Ralstonia eutropha Strain Bo

2001 ◽  
Vol 183 (6) ◽  
pp. 1954-1960 ◽  
Author(s):  
Grit Zarnt ◽  
Thomas Schräder ◽  
Jan R. Andreesen
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Alcohol Dehydrogenase ◽  
Tertiary Structure ◽  
Ralstonia Eutropha ◽  
Signal Sequence ◽  
Substrate Inhibition ◽  
Catalytic Efficiency ◽  
Gene Encoding

ABSTRACT The quinohemoprotein tetrahydrofurfuryl alcohol dehydrogenase (THFA-DH) from Ralstonia eutropha strain Bo was investigated for its catalytic properties. The apparentk cat/Km andK i values for several substrates were determined using ferricyanide as an artificial electron acceptor. The highest catalytic efficiency was obtained with n-pentanol exhibiting a k cat/Km value of 788 × 104 M−1 s−1. The enzyme showed substrate inhibition kinetics for most of the alcohols and aldehydes investigated. A stereoselective oxidation of chiral alcohols with a varying enantiomeric preference was observed. Initial rate studies using ethanol and acetaldehyde as substrates revealed that a ping-pong mechanism can be assumed for in vitro catalysis of THFA-DH. The gene encoding THFA-DH from R. eutropha strain Bo (tfaA) has been cloned and sequenced. The derived amino acid sequence showed an identity of up to 67% to the sequence of various quinoprotein and quinohemoprotein dehydrogenases. A comparison of the deduced sequence with the N-terminal amino acid sequence previously determined by Edman degradation analysis suggested the presence of a signal sequence of 27 residues. The primary structure of TfaA indicated that the protein has a tertiary structure quite similar to those of other quinoprotein dehydrogenases.

Oxidative Modification of Fibrinogen Affects Its Binding Activity to Glycoprotein (GP) IIb/IIIa

2009 ◽  
Vol 16 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Sermin Tetik ◽  
Kurtulus Kaya ◽  
M. Demir ◽  
Emel Eksioglu-Demiralp ◽  
Turay Yardimci
Keyword(s):  
Metal Ion ◽  
Degradation Products ◽  
Binding Capacity ◽  
Protein Structures ◽  
Human Platelets ◽  
Binding Activity ◽  
Oxidative Modification ◽  
Oxidized Fibrinogen ◽  
Protein Functions

Aim: Proteins are sensitive biomarkers of human diease condition associated with oxidative stress. Alteration of protein structures by oxidants may result in partial or complete loss of protein functions. We have investigated the effect of structural modifications induced by metal ion catalyzed oxidation of fibrinogen on its binding capacity to glycoprotein IIb/IIIa (GpIIb/IIIa) and human platelets. Methods: We identified and quantified of binding capacity of native and oxidized fibrinogen to its receptor in vitro by flow cytometer. Dityrosine formation on oxidized fibrinogen were detected spectrophotometrically. Elevated degradation products of fibrinogen after oxidation were revealed in the HPLC analysis. The native and oxidized fibrinogen were analyzed on mass spectrum upon digestion with tyripsin. Results: Oxidatively modified fibrinogen showed less binding activity than native fibrinogen to GpIIb/IIIa coated micro beads and human platelets whereas slightly higher binding capaticity to ADP induced stimulated platelets. Formation of dityrosines in the amino acid side chains of fibrinogen were observed upon oxidation. Decreased binding capacity of oxidized fibrinogen correlated with intensities of dityrosine formation. Oxidized fibrinogen had more ion-mass intensities at higher than native fibrinogen. Clinical implications: Important point is decreased of binding capacity of the oxidized fibrinogen to own receptor. The decreased rate of binding, leading to effect in the diseases of clot formation may acount for the association between oxidation of fibrinogen and the incidence of effect in human diseases.

scholarly journals A microwave-catalyzed rapid, efficient and ecofriendly synthesis of substituted pyrazol-5-ones (Short communication)

2003 ◽  
Vol 68 (10) ◽  
pp. 723-727 ◽  
Author(s):  
Vijay Dabholkar ◽  
Rahul Gavande
Keyword(s):  
Acetic Acid ◽  
Carboxylic Acid ◽  
Microwave Irradiation ◽  
Reaction Rate ◽  
Short Communication ◽  
Acid Hydrazide ◽  
Acetoacetic Ester ◽  
Carboxylic Acid Hydrazide ◽  
Conventional Methods

A series of 1-(3,4-dihydro-3-oxo-2H-1,4-benzoxazine-2-carbonyl)-3-methyl-4-(substituted phenylhydrazono)-2-pyrazolin-5-ones have been synthesized by the reaction of 2H-3,4-dihydro-3-oxo-1,4-benzoxazine-2-carboxylic acid hydrazide with substituted acetoacetic ester derivatives using acetic acid as solvent under microwave irradiation (MWI), as well as by conventional methods. The reaction rate is enhanced tremendously and the yields are improved under MWI as compared to conventional methods.

scholarly journals Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Michael Stumpp
Keyword(s):  
Single Agent ◽  
Standard Of Care ◽  
Cooperative Binding ◽  
Wild Type ◽  
Inhibitory Potency ◽  
Alpha Variant ◽  
The Individual ◽  
Very High ◽  
Comprehensive Study

Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron, as of December 2021. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

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