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Patrick C Wilson - One of the best experts on this subject based on the ideXlab platform.
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hemagglutinin stalk reactive antibodies interfere with influenza virus neuraminidase activity by Steric Hindrance
Journal of Virology, 2018Co-Authors: Yaoqing Chen, Linda Yuling Lan, Min Huang, Carole Henry, Patrick C WilsonAbstract:Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current "one-shot" universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA stalk-reactive antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) was evident for an attached substrate but not for unattached small-molecule cleavage of sialic acid. This finding suggests that the antibodies inhibit NA enzymatic activity through Steric Hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab')2 fragments that occupied reduced area without loss of avidity or disrupted HA/NA interactions showed significantly reduced NI activity. Notably, HA stalk-binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of protection mediated by HA stalk-reactive antibodies.IMPORTANCE This study reports a new mechanism of protection mediated by influenza hemagglutinin stalk-reactive antibodies, i.e., inhibition of neuraminidase activity by Steric Hindrance, blocking access of neuraminidase to sialic acids when it abuts hemagglutinin on whole virions.
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hemagglutinin stalk reactive antibodies interfere with influenza virus neuraminidase activity by Steric Hindrance
bioRxiv, 2018Co-Authors: Yaoqing Chen, Linda Yuling Lan, Min Huang, Carole Henry, Patrick C WilsonAbstract:Abstract: Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current “one-shot” universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA-stalk antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) is evident for an attached substrate but not for unattached small molecule cleavage of sialic acid. This suggests that the antibodies inhibit NA enzymatic activity through Steric Hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab’)2 fragments that occupy reduced area without loss of avidity or disrupted HA/NA interactions show significantly reduced NI activity. Notably, HA stalk binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of HA-stalk antibody mediated protection. Summary This study reports a new mechanism of protection that is mediated by influenza hemagglutinin-stalk reactive antibodies: inhibition of neuraminidase activity by Steric Hindrance, blocking access of neuraminidase to sialic acids when it is abutted next to hemagglutinin on whole virions.
Yaoqing Chen - One of the best experts on this subject based on the ideXlab platform.
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hemagglutinin stalk reactive antibodies interfere with influenza virus neuraminidase activity by Steric Hindrance
Journal of Virology, 2018Co-Authors: Yaoqing Chen, Linda Yuling Lan, Min Huang, Carole Henry, Patrick C WilsonAbstract:Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current "one-shot" universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA stalk-reactive antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) was evident for an attached substrate but not for unattached small-molecule cleavage of sialic acid. This finding suggests that the antibodies inhibit NA enzymatic activity through Steric Hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab')2 fragments that occupied reduced area without loss of avidity or disrupted HA/NA interactions showed significantly reduced NI activity. Notably, HA stalk-binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of protection mediated by HA stalk-reactive antibodies.IMPORTANCE This study reports a new mechanism of protection mediated by influenza hemagglutinin stalk-reactive antibodies, i.e., inhibition of neuraminidase activity by Steric Hindrance, blocking access of neuraminidase to sialic acids when it abuts hemagglutinin on whole virions.
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hemagglutinin stalk reactive antibodies interfere with influenza virus neuraminidase activity by Steric Hindrance
bioRxiv, 2018Co-Authors: Yaoqing Chen, Linda Yuling Lan, Min Huang, Carole Henry, Patrick C WilsonAbstract:Abstract: Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current “one-shot” universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA-stalk antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) is evident for an attached substrate but not for unattached small molecule cleavage of sialic acid. This suggests that the antibodies inhibit NA enzymatic activity through Steric Hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab’)2 fragments that occupy reduced area without loss of avidity or disrupted HA/NA interactions show significantly reduced NI activity. Notably, HA stalk binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of HA-stalk antibody mediated protection. Summary This study reports a new mechanism of protection that is mediated by influenza hemagglutinin-stalk reactive antibodies: inhibition of neuraminidase activity by Steric Hindrance, blocking access of neuraminidase to sialic acids when it is abutted next to hemagglutinin on whole virions.
Sahar Sadat Mahshid - One of the best experts on this subject based on the ideXlab platform.
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Biomolecular Steric Hindrance Effects Are Enhanced on Nanostructured Microelectrodes
Analytical chemistry, 2017Co-Authors: Sahar Sadat Mahshid, Alexis Vallée-bélisle, Shana O. KelleyAbstract:The availability of rapid approaches for quantitative detection of biomarkers would drastically impact global health by enabling decentralized disease diagnosis anywhere that patient care is administered. A promising new approach, the electrochemical Steric Hindrance hybridization assay (eSHHA) has been introduced for quantitative detection of large proteins (e.g., antibodies) with a low nanomolar detection limit within 10 min. Here, we report the use of a nanostructured microelectrode (NME) platform for eSHHA that improves the performance of this approach by increasing the efficiency and kinetics of DNA hybridization. We demonstrated that eSHHA on nanostructured microelectrodes leverages three effects: (1) Steric Hindrance effects at the nanoscale, (2) a size-dependent hybridization rate of DNA complexes, and (3) electrode morphology-dependent blocking effects. As a proof of concept, we showed that the sensitivity of eSHHA toward a model antibody is enhanced using NMEs as scaffolds for this reaction. We ...
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a highly selective electrochemical dna based sensor that employs Steric Hindrance effects to detect proteins directly in whole blood
Journal of the American Chemical Society, 2015Co-Authors: Sahar Sadat Mahshid, Sebastien Camire, Francesco Ricci, Alexis ValleebelisleAbstract:Here we describe a highly selective DNA-based electrochemical sensor that utilizes Steric Hindrance effects to signal the presence of large macromolecules in a single-step procedure. We first show that a large macromolecule, such as a protein, when bound to a signaling DNA strand generates Steric Hindrance effects, which limits the ability of this DNA to hybridize to a surface-attached complementary strand. We demonstrate that the efficiency of hybridization of this signaling DNA is inversely correlated with the size of the molecule attached to it, following a semilogarithmic relationship. Using this Steric Hindrance hybridization assay in an electrochemical format (eSHHA), we demonstrate the multiplexed, quantitative, one-step detection of various macromolecules in the low nanomolar range, in <10 min directly in whole blood. We discuss the potential applications of this novel signaling mechanism in the field of point-of-care diagnostic sensors.
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A Highly Selective Electrochemical DNA-Based Sensor That Employs Steric Hindrance Effects to Detect Proteins Directly in Whole Blood.
Journal of the American Chemical Society, 2015Co-Authors: Sahar Sadat Mahshid, Sebastien Camire, Francesco Ricci, Alexis Vallée-bélisleAbstract:Here we describe a highly selective DNA-based electrochemical sensor that utilizes Steric Hindrance effects to signal the presence of large macromolecules in a single-step procedure. We first show that a large macromolecule, such as a protein, when bound to a signaling DNA strand generates Steric Hindrance effects, which limits the ability of this DNA to hybridize to a surface-attached complementary strand. We demonstrate that the efficiency of hybridization of this signaling DNA is inversely correlated with the size of the molecule attached to it, following a semilogarithmic relationship. Using this Steric Hindrance hybridization assay in an electrochemical format (eSHHA), we demonstrate the multiplexed, quantitative, one-step detection of various macromolecules in the low nanomolar range, in
Yanan Zhao - One of the best experts on this subject based on the ideXlab platform.
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Steric Hindrance effect on amine demonstrated in solid polymer membranes for CO2 transport
Journal of Membrane Science, 2012Co-Authors: Yanan ZhaoAbstract:Abstract Due to Steric Hindrance effect, aqueous solutions of Sterically hindered amines have demonstrated superior advantages for carbon dioxide absorption over unhindered amines and hence have been used in commercial gas treating processes to remove CO 2 from syngas and natural gas. This work for the first time reports the effect of amine Steric Hindrance demonstrated in a solid phase. The Steric Hindrance effect dramatically enhanced the CO 2 transport of hindered polyamines in the solid polymeric matrix of new fixed-site-carrier facilitated transport membranes synthesized by blending hindered polyamines with crosslinked polyvinylalcohol. The new membranes exhibited significantly improved CO 2 /H 2 and CO 2 /N 2 separation performances at 110 °C and a feed pressure of 2 atm. This work could provide significant opportunities for further fundamental work to fully exploit Sterically hindered amines and open a new approach for the development of next generation gas separation membranes.
Hiroaki Gotoh - One of the best experts on this subject based on the ideXlab platform.
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A theoretical, dynamical evaluation method of the Steric Hindrance in nitroxide radicals using transition states of model reactions
Scientific Reports, 2019Co-Authors: Yudai Yamazaki, Jun Naganuma, Hiroaki GotohAbstract:Steric Hindrance is known to affect the stability, reactivity, and radical trapping ability of stable nitroxide radicals. Therefore, a quantitative evaluation and prediction model of Steric Hindrance is needed to select and design the optimum nitroxide radicals for specific applications. In this study, a dynamic parameter of Steric Hindrance (DPSH) is proposed and its characteristics are investigated. Unlike using only the equilibrium structure to evaluate the Steric Hindrance, DPSH is a dynamic value calculated from the theoretical activation enthalpies for two model reactions of radical addition to olefins. Using DPSH, the Steric Hindrance was evaluated for a total of 43 alkyl radicals, nitroxide radicals, and radicals derived from phenols, and the results were compared with those of other methods. The DPSH values for radicals can vary when the energy barrier for structural change varies, even if the equilibrium structures of the radicals have the same Steric shielding. Finally, for radicals other than nitroxide radicals, the DPSH values were consistent with the predictions from their structures, which suggests that the DPSH has a wide range of applications. We expect DPSH to be used and developed in the analysis of Steric factors in various reactions.
