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@article{2364863,
author = {Vilím, Jan and Ghazalová, Tereza and Petulová, Eliška and Horackova, Aneta and Stepankova, Veronika and Chaloupková, Radka and Bednář, David and Damborský, Jiří and Prokop, Zbyněk},
article_location = {AMSTERDAM},
article_number = {October 2023},
doi = {http://dx.doi.org/10.1016/j.csbj.2023.10.009},
keywords = {Computer-assisted stabilization; Fibroblast growth factor; Thermostability; Resistance to; Protease; Improved yield; FGF-18},
language = {eng},
issn = {2001-0370},
journal = {Computational and Structural Biotechnology Journal},
title = {Computer-assisted stabilization of fibroblast growth factor FGF-18},
url = {https://www.sciencedirect.com/science/article/pii/S2001037023003665?via%3Dihub},
volume = {21},
year = {2023}
}
TY - JOUR
ID - 2364863
AU - Vilím, Jan - Ghazalová, Tereza - Petulová, Eliška - Horackova, Aneta - Stepankova, Veronika - Chaloupková, Radka - Bednář, David - Damborský, Jiří - Prokop, Zbyněk
PY - 2023
TI - Computer-assisted stabilization of fibroblast growth factor FGF-18
JF - Computational and Structural Biotechnology Journal
VL - 21
IS - October 2023
SP - 5144-5152
EP - 5144-5152
PB - Elsevier
SN - 20010370
KW - Computer-assisted stabilization
KW - Fibroblast growth factor
KW - Thermostability
KW - Resistance to
KW - Protease
KW - Improved yield
KW - FGF-18
UR - https://www.sciencedirect.com/science/article/pii/S2001037023003665?via%3Dihub
N2 - The fibroblast growth factors (FGF) family holds significant potential for addressing chronic diseases. Specifically, recombinant FGF18 shows promise in treating osteoarthritis by stimulating cartilage formation. However, recent phase 2 clinical trial results of sprifermin (recombinant FGF18) indicate insufficient efficacy. Leveraging our expertise in rational protein engineering, we conducted a study to enhance the stability of FGF18. As a result, we obtained a stabilized variant called FGF18-E4, which exhibited improved stability with 16 degrees C higher melting temperature, resistance to trypsin and a 2.5-fold increase in production yields. Moreover, the FGF18-E4 maintained mitogenic activity after 1-week incubation at 37 degrees C and 1-day at 50 degrees C. Additionally, the inserted mutations did not affect its binding to the fibroblast growth factor receptors, making FGF18-E4 a promising candidate for advancing FGF-based osteoarthritis treatment.
ER -
VILÍM, Jan, Tereza GHAZALOVÁ, Eliška PETULOVÁ, Aneta HORACKOVA, Veronika STEPANKOVA, Radka CHALOUPKOVÁ, David BEDNÁŘ, Jiří DAMBORSKÝ a Zbyněk PROKOP. Computer-assisted stabilization of fibroblast growth factor FGF-18. \textit{Computational and Structural Biotechnology Journal}. AMSTERDAM: Elsevier, 2023, roč.~21, October 2023, s.~5144-5152. ISSN~2001-0370. Dostupné z: https://dx.doi.org/10.1016/j.csbj.2023.10.009.
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