Insights on the Formulation of Recombinant Proteins

Ribeiro, Rita; Abreu, Teresa; Silva, Ana Catarina; Gonçalves, João; Moreira, João Nuno

doi:10.1007/10_2019_119

Cited by 6 publications

(3 citation statements)

References 120 publications

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“…Drug research on GPCRs is mainly focused on the design, production, and purification of recombinant proteins and cloned antibodies. [43][44][45] Similar to previous studies, GPR56 NTF mutation or blockade by recombinant NTF protein inhibited the biological effects of GPR56. 16,17 Taking into account the short half-life and immunogen-mediated antidrug response of recombinant proteins, we used clonal antibodies with a highly specific and long-circulating plasma half-life and a low risk of adverse clinical side effects 45 to perform in vitro experiments.…”

Section: Discussionsupporting

confidence: 85%

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Role of GPR56 in Platelet Activation and Arterial Thrombosis

Zhang

et al. 2022

Thromb Haemost

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The adhesion G protein-coupled receptor GPR56 mediates cell-cell and cell-extracellular matrix interactions. To examine the function of GPR56 in platelet activation and arterial thrombosis, we generated GPR56-knockout mice and evaluated GPR56 expression in human and mouse platelets. The results revealed that the levels of the GPR56 N-terminal fragment were significantly higher on the first day after myocardial infarction than on the seventh day in the plasma of patients with ST-segment-elevation myocardial infarction. Next, we investigated the effects of GPR56 on platelet function in vitro and in vivo. We observed that collagen-induced aggregation and adenosine triphosphate release were reduced in Gpr56-/- platelets. Furthermore, P-selectin expression on the Gpr56-/- platelet surface was also reduced, and the spreading area on immobilized collagen was decreased in Gpr56-/- platelets. Furthermore, collagen-induced platelet activation in human platelets was inhibited by an anti-GPR56 antibody. Gpr56-/- mice showed an extended time to the first occlusion in models with cremaster arteriole laser injury and FeCl3-induced carotid artery injury. GPR56 activated the G protein 13 signaling pathway following collagen stimulation, which promoted platelet adhesion and thrombus formation at the site of vascular injury. Thus, our study confirmed that GPR56 regulated the formation of arterial thrombosis. Inhibition of the initial response of GPR56 to collagen could significantly inhibit platelet activation and thrombus formation. Our results provide new insights for research into antiplatelet drugs.

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Section: Discussionsupporting

confidence: 85%

“…primarily focus on collagen receptors. Drug research on GPCRs is mainly focused on the design, production, and purification of recombinant proteins and cloned antibodies [43][44][45] . Similar to previous studies, GPR56 NTF mutation or blockade by recombinant NTF protein inhibited the biological effects of GPR56 16,17 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Role of GPR56 in Platelet Activation and Arterial Thrombosis

Zhang

et al. 2022

Thromb Haemost

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“…By their intrinsic nature, protein-based drugs are extremely sensitive to physical and chemical environmental factors such as temperature, shear-forces, light, pH, glycosylation, and enzymatic action Rajan et al, 2021 . Hence, probing protein aggregation during the development and manufacturing of protein-based drugs is essential to achieve a final product that is not only stable for long-term storage but also harbors fewer impurities that stimulate an anti-drug immune response ( Ratanji et al, 2014 ; Svilenov et al, 2018 ; Ribeiro et al, 2019 ). Finally, production of high-quality protein is also important in many other industrial applications such as agriculture, food and beverage processing, production of cosmetics and biofuels, and in biotechnology applications such as biosensors and optogenetics ( Zhang and Cohen, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Measuring Protein Aggregation and Stability Using High-Throughput Biophysical Approaches

Kwan

Kolek

Danson

et al. 2022

Front. Mol. Biosci.

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Structure-function relationships of biological macromolecules, in particular proteins, provide crucial insights for fundamental biochemistry, medical research and early drug discovery. However, production of recombinant proteins, either for structure determination, functional studies, or to be used as biopharmaceutical products, is often hampered by their instability and propensity to aggregate in solution in vitro. Protein samples of poor quality are often associated with reduced reproducibility as well as high research and production expenses. Several biophysical methods are available for measuring protein aggregation and stability. Yet, discovering and developing means to improve protein behaviour and structure-function integrity remains a demanding task. Here, we discuss workflows that are made possible by adapting established biophysical methods to high-throughput screening approaches. Rapid identification and optimisation of conditions that promote protein stability and reduce aggregation will support researchers and industry to maximise sample quality, stability and reproducibility, thereby reducing research and development time and costs.

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Administration of Biologicals

Silva

2024

SpringerBriefs in Molecular Science

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Insights on the Formulation of Recombinant Proteins

Cited by 6 publications

References 120 publications

Role of GPR56 in Platelet Activation and Arterial Thrombosis

Role of GPR56 in Platelet Activation and Arterial Thrombosis

Measuring Protein Aggregation and Stability Using High-Throughput Biophysical Approaches

Administration of Biologicals

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