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323 results on '"RICHTER W."'

6. Protein engineering of a stable and potent anti-inflammatory IL-37-Fc fusion with enhanced therapeutic potential.

Author

Bujotzek A., Tiefenthaler G., Lariviere L., D'Andrea L., Marquez E.A., Rudloff I., Cho S.X., Deen N.S., Richter W., Regenass-Lechner F., Poehler A., Whisstock J.C., Sydow-Andersen J., Reiser X., Schuster S., Neubauer J., Hoepfl S., Richter K., Nold M.F., Nold-Petry C.A., Schumacher F., Ellisdon A.M., Bujotzek A., Tiefenthaler G., Lariviere L., D'Andrea L., Marquez E.A., Rudloff I., Cho S.X., Deen N.S., Richter W., Regenass-Lechner F., Poehler A., Whisstock J.C., Sydow-Andersen J., Reiser X., Schuster S., Neubauer J., Hoepfl S., Richter K., Nold M.F., Nold-Petry C.A., Schumacher F., and Ellisdon A.M.

Abstract

Harnessing the immunomodulatory activity of cytokines is a focus of therapies targeting inflammatory disease. The interleukin (IL)-1 superfamily contains pro-inflammatory and anti-inflammatory members that help orchestrate the immune response in adaptive and innate immunity. Of these molecules, IL-37 has robust anti-inflammatory activity across a range of disease models through inhibition of pro-inflammatory signaling cascades downstream of tumor necrosis factor, IL-1, and toll-like receptor pathways. We find that IL-37 is unstable with a poor pharmacokinetic and manufacturing profile. Here, we present the engineering of IL-37 from an unstable cytokine into an anti-inflammatory molecule with an excellent therapeutic likeness. We overcame these shortcomings through site-directed mutagenesis, the addition of a non-native disulfide bond, and the engineering of IL-37 as an Fc-fusion protein. Our results provide a platform for preclinical testing of IL-37 Fc-fusion proteins. The engineering approaches undertaken herein will apply to the conversion of similar potent yet short-acting cytokines into therapeutics.Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.

Published
2021

7. Protein engineering of a stable and potent anti-inflammatory IL-37-Fc fusion with enhanced therapeutic potential.

Author

Bujotzek A., Tiefenthaler G., Lariviere L., D'Andrea L., Marquez E.A., Rudloff I., Cho S.X., Deen N.S., Richter W., Regenass-Lechner F., Poehler A., Whisstock J.C., Sydow-Andersen J., Reiser X., Schuster S., Neubauer J., Hoepfl S., Richter K., Nold M.F., Nold-Petry C.A., Schumacher F., Ellisdon A.M., Bujotzek A., Tiefenthaler G., Lariviere L., D'Andrea L., Marquez E.A., Rudloff I., Cho S.X., Deen N.S., Richter W., Regenass-Lechner F., Poehler A., Whisstock J.C., Sydow-Andersen J., Reiser X., Schuster S., Neubauer J., Hoepfl S., Richter K., Nold M.F., Nold-Petry C.A., Schumacher F., and Ellisdon A.M.

Abstract

Harnessing the immunomodulatory activity of cytokines is a focus of therapies targeting inflammatory disease. The interleukin (IL)-1 superfamily contains pro-inflammatory and anti-inflammatory members that help orchestrate the immune response in adaptive and innate immunity. Of these molecules, IL-37 has robust anti-inflammatory activity across a range of disease models through inhibition of pro-inflammatory signaling cascades downstream of tumor necrosis factor, IL-1, and toll-like receptor pathways. We find that IL-37 is unstable with a poor pharmacokinetic and manufacturing profile. Here, we present the engineering of IL-37 from an unstable cytokine into an anti-inflammatory molecule with an excellent therapeutic likeness. We overcame these shortcomings through site-directed mutagenesis, the addition of a non-native disulfide bond, and the engineering of IL-37 as an Fc-fusion protein. Our results provide a platform for preclinical testing of IL-37 Fc-fusion proteins. The engineering approaches undertaken herein will apply to the conversion of similar potent yet short-acting cytokines into therapeutics.Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.

Published
2021

17. Constraining the Neutron Star Compactness: Extraction of the $^{23}$Al($p,\gamma$) Reaction Rate for the $rp$-Process

Author

Wolf, C., Langer, C., Montes, F., Pereira, J., Ong, W. -J., Poxon-Pearson, T., Ahn, S., Ayoub, S., Baumann, T., Bazin, D., Bender, P. C., Brown, B. A., Browne, J., Crawford, H., Cyburt, R. H., Deleeuw, E., Elman, B., Fiebiger, S., Gade, A., Gastis, P., Lipschutz, S., Longfellow, B., Meisel, Z., Nunes, F. M., Perdikakis, G., Reifarth, R., Richter, W. A., Schatz, H., Schmidt, K., Schmitt, J., Sullivan, C., Titus, R., Weisshaar, D., Woods, P. J., Zamora, J. C., Zegers, R. G. T., Wolf, C., Langer, C., Montes, F., Pereira, J., Ong, W. -J., Poxon-Pearson, T., Ahn, S., Ayoub, S., Baumann, T., Bazin, D., Bender, P. C., Brown, B. A., Browne, J., Crawford, H., Cyburt, R. H., Deleeuw, E., Elman, B., Fiebiger, S., Gade, A., Gastis, P., Lipschutz, S., Longfellow, B., Meisel, Z., Nunes, F. M., Perdikakis, G., Reifarth, R., Richter, W. A., Schatz, H., Schmidt, K., Schmitt, J., Sullivan, C., Titus, R., Weisshaar, D., Woods, P. J., Zamora, J. C., and Zegers, R. G. T.

Abstract

The $^{23}$Al($p,\gamma$)$^{24}$Si reaction is among the most important reactions driving the energy generation in Type-I X-ray bursts. However, the present reaction-rate uncertainty limits constraints on neutron star properties that can be achieved with burst model-observation comparisons. Here, we present a novel technique for constraining this important reaction by combining the GRETINA array with the neutron detector LENDA coupled to the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The $^{23}$Al($d,n$) reaction was used to populate the astrophysically important states in $^{24}$Si. This enables a measurement in complete kinematics for extracting all relevant inputs necessary to calculate the reaction rate. For the first time, a predicted close-lying doublet of a 2$_2^+$ and (4$_1^+$,0$_2^+$) state in $^{24}$Si was disentangled, finally resolving conflicting results from two previous measurements. Moreover, it was possible to extract spectroscopic factors using GRETINA and LENDA simultaneously. This new technique may be used to constrain other important reaction rates for various astrophysical scenarios.

Published
2019
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22. Constraining the Neutron Star Compactness: Extraction of the $^{23}$Al($p,\gamma$) Reaction Rate for the $rp$-Process

Author

Wolf, C., Langer, C., Montes, F., Pereira, J., Ong, W. -J., Poxon-Pearson, T., Ahn, S., Ayoub, S., Baumann, T., Bazin, D., Bender, P. C., Brown, B. A., Browne, J., Crawford, H., Cyburt, R. H., Deleeuw, E., Elman, B., Fiebiger, S., Gade, A., Gastis, P., Lipschutz, S., Longfellow, B., Meisel, Z., Nunes, F. M., Perdikakis, G., Reifarth, R., Richter, W. A., Schatz, H., Schmidt, K., Schmitt, J., Sullivan, C., Titus, R., Weisshaar, D., Woods, P. J., Zamora, J. C., Zegers, R. G. T., Wolf, C., Langer, C., Montes, F., Pereira, J., Ong, W. -J., Poxon-Pearson, T., Ahn, S., Ayoub, S., Baumann, T., Bazin, D., Bender, P. C., Brown, B. A., Browne, J., Crawford, H., Cyburt, R. H., Deleeuw, E., Elman, B., Fiebiger, S., Gade, A., Gastis, P., Lipschutz, S., Longfellow, B., Meisel, Z., Nunes, F. M., Perdikakis, G., Reifarth, R., Richter, W. A., Schatz, H., Schmidt, K., Schmitt, J., Sullivan, C., Titus, R., Weisshaar, D., Woods, P. J., Zamora, J. C., and Zegers, R. G. T.

Abstract

The $^{23}$Al($p,\gamma$)$^{24}$Si reaction is among the most important reactions driving the energy generation in Type-I X-ray bursts. However, the present reaction-rate uncertainty limits constraints on neutron star properties that can be achieved with burst model-observation comparisons. Here, we present a novel technique for constraining this important reaction by combining the GRETINA array with the neutron detector LENDA coupled to the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The $^{23}$Al($d,n$) reaction was used to populate the astrophysically important states in $^{24}$Si. This enables a measurement in complete kinematics for extracting all relevant inputs necessary to calculate the reaction rate. For the first time, a predicted close-lying doublet of a 2$_2^+$ and (4$_1^+$,0$_2^+$) state in $^{24}$Si was disentangled, finally resolving conflicting results from two previous measurements. Moreover, it was possible to extract spectroscopic factors using GRETINA and LENDA simultaneously. This new technique may be used to constrain other important reaction rates for various astrophysical scenarios.

Published
2019
Full Text
View/download PDF

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