Novel protein scaffolds as emerging therapeutic proteins: from discovery to clinical proof-of-concept

2012 ◽  
Vol 30 (11) ◽  
pp. 575-582 ◽  
Author(s):  
Thierry Wurch ◽  
Alain Pierré ◽  
Stéphane Depil
Keyword(s):  
Therapeutic Proteins ◽  
Protein Scaffolds ◽  
Proof Of Concept ◽  
Novel Protein

Recent advances in the development of novel protein scaffolds based therapeutics

2017 ◽  
Vol 102 ◽  
pp. 630-641 ◽  
Author(s):  
Asim Azhar ◽  
Ejaj Ahmad ◽  
Qamar Zia ◽  
Mohd. Ahmar Rauf ◽  
Mohammad Owais ◽  
...  
Keyword(s):  
Protein Scaffolds ◽  
Recent Advances ◽  
Novel Protein

scholarly journals A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ami Miller ◽  
Adam Leach ◽  
Jemima Thomas ◽  
Craig McAndrew ◽  
Emma Bentley ◽  
...  
Keyword(s):  
Virus Infection ◽  
P53 Protein ◽  
Therapeutic Proteins ◽  
Spike Protein ◽  
Engineering Technology ◽  
Angiotensin Converting Enzyme 2 ◽  
Self Assembling ◽  
Promising Strategy ◽  
Tetramerization Domain ◽  
Novel Protein

AbstractApproaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.

Biopharmaceutical drug discovery using novel protein scaffolds

2006 ◽  
Vol 17 (6) ◽  
pp. 653-658 ◽  
Author(s):  
Davinder S Gill ◽  
Nitin K Damle
Keyword(s):  
Drug Discovery ◽  
Protein Scaffolds ◽  
Novel Protein

Proof of Concept To Achieve Infinite Selectivity for the Chromatographic Separation of Therapeutic Proteins

2019 ◽  
Vol 91 (20) ◽  
pp. 12954-12961 ◽  
Author(s):  
Szabolcs Fekete ◽  
Alain Beck ◽  
Jean-Luc Veuthey ◽  
Davy Guillarme
Keyword(s):  
Chromatographic Separation ◽  
Therapeutic Proteins ◽  
Proof Of Concept

scholarly journals Non-Antibody-Based Binders for the Enrichment of Proteins for Analysis by Mass Spectrometry

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1791
Author(s):  
Oladapo Olaleye ◽  
Natalia Govorukhina ◽  
Nico C. van de Merbel ◽  
Rainer Bischoff
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Therapeutic Proteins ◽  
Body Fluids ◽  
Protein Scaffolds ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Ms Analysis ◽  
Development And Validation

There is often a need to isolate proteins from body fluids, such as plasma or serum, prior to further analysis with (targeted) mass spectrometry. Although immunoglobulin or antibody-based binders have been successful in this regard, they possess certain disadvantages, which stimulated the development and validation of alternative, non-antibody-based binders. These binders are based on different protein scaffolds and are often selected and optimized using phage or other display technologies. This review focuses on several non-antibody-based binders in the context of enriching proteins for subsequent liquid chromatography-mass spectrometry (LC-MS) analysis and compares them to antibodies. In addition, we give a brief introduction to approaches for the immobilization of binders. The combination of non-antibody-based binders and targeted mass spectrometry is promising in areas, like regulated bioanalysis of therapeutic proteins or the quantification of biomarkers. However, the rather limited commercial availability of these binders presents a bottleneck that needs to be addressed.

scholarly journals A Super-Potent Tetramerized ACE2 Protein Displays Enhanced Neutralization of SARS-CoV-2 Virus Infection

2021 ◽  
Author(s):  
Ami Miller ◽  
Adam Leach ◽  
Jemima Thomas ◽  
Emma Bentley ◽  
Giada Mattiuzzo ◽  
...  
Keyword(s):  
Virus Infection ◽  
P53 Protein ◽  
Therapeutic Proteins ◽  
Spike Protein ◽  
Engineering Technology ◽  
Angiotensin Converting Enzyme 2 ◽  
Self Assembling ◽  
Promising Strategy ◽  
Tetramerization Domain ◽  
Novel Protein

Abstract Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin g1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.

C5-O-02Targeted Imaging and Theranostics with Peptides and Novel Protein Scaffolds, Repebody and Monobody

Microscopy ◽  
2015 ◽  
Vol 64 (suppl 1) ◽  
pp. i72.1-i72
Author(s):  
Misun Yun ◽  
Seung Hwan Park ◽  
Yeongjin Hong ◽  
Jung-Joon Min
Keyword(s):  
Protein Scaffolds ◽  
Novel Protein

Direct measurement of electron-diffraction-pattern intensities using an energy loss spectrometer

1989 ◽  
Vol 47 ◽  
pp. 668-669
Author(s):  
A. G. Jackson ◽  
M. Rowe
Keyword(s):  
Thermal Effects ◽  
Dynamic Range ◽  
Scattering Amplitude ◽  
Dynamical Theory ◽  
Site Symmetry ◽  
Proof Of Concept ◽  
Parallel Acquisition ◽  
Kinematic Approximation ◽  
Speed Up ◽  
Structure Calculations

Diffraction intensities from intermetallic compounds are, in the kinematic approximation, proportional to the scattering amplitude from the element doing the scattering. More detailed calculations have shown that site symmetry and occupation by various atom species also affects the intensity in a diffracted beam. [1] Hence, by measuring the intensities of beams, or their ratios, the occupancy can be estimated. Measurement of the intensity values also allows structure calculations to be made to determine the spatial distribution of the potentials doing the scattering. Thermal effects are also present as a background contribution. Inelastic effects such as loss or absorption/excitation complicate the intensity behavior, and dynamical theory is required to estimate the intensity value.The dynamic range of currents in diffracted beams can be 104or 105:1. Hence, detection of such information requires a means for collecting the intensity over a signal-to-noise range beyond that obtainable with a single film plate, which has a S/N of about 103:1. Although such a collection system is not available currently, a simple system consisting of instrumentation on an existing STEM can be used as a proof of concept which has a S/N of about 255:1, limited by the 8 bit pixel attributes used in the electronics. Use of 24 bit pixel attributes would easily allowthe desired noise range to be attained in the processing instrumentation. The S/N of the scintillator used by the photoelectron sensor is about 106 to 1, well beyond the S/N goal. The trade-off that must be made is the time for acquiring the signal, since the pattern can be obtained in seconds using film plates, compared to 10 to 20 minutes for a pattern to be acquired using the digital scan. Parallel acquisition would, of course, speed up this process immensely.

Remote Echocardiography: Proof of Concept for Support of National Disasters, Combat and Humanitarian Mission

2002 ◽  
Author(s):  
Sheri Yvonne Nottestad Boyd ◽  
Linda L. Huffer ◽  
Terry D. Bauch ◽  
James L. Furgerson
Keyword(s):  
Proof Of Concept ◽  
Humanitarian Mission
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