Computer-assisted stabilization of fibroblast growth factor
FGF-18

J 2023

Computer-assisted stabilization of fibroblast growth factor FGF-18

VILÍM, Jan, Tereza GHAZALOVÁ, Eliška PETULOVÁ, Aneta HORACKOVA, Veronika STEPANKOVA et. al.

Basic information

Original name

Computer-assisted stabilization of fibroblast growth factor FGF-18

Authors

VILÍM, Jan (203 Czech Republic, belonging to the institution), Tereza GHAZALOVÁ (203 Czech Republic), Eliška PETULOVÁ (203 Czech Republic), Aneta HORACKOVA, Veronika STEPANKOVA, Radka CHALOUPKOVÁ (203 Czech Republic), David BEDNÁŘ (203 Czech Republic, belonging to the institution), Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution) and Zbyněk PROKOP (203 Czech Republic, belonging to the institution)

Edition

Computational and Structural Biotechnology Journal, AMSTERDAM, Elsevier, 2023, 2001-0370

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.000 in 2022

RIV identification code

RIV/00216224:14310/23:00133177

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.csbj.2023.10.009

UT WoS

001097281900001

Keywords in English

Computer-assisted stabilization; Fibroblast growth factor; Thermostability; Resistance to; Protease; Improved yield; FGF-18

Abstract

V originále

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.

Links

EF18_053/0016952, research and development project

Name: Postdoc2MUNI

FW03010208, research and development project

Name: Stabilizace aplikačně atraktivních FGF proteinů pomocí pokročilých automatizovaných metod proteinového inženýrství

Investor: Technology Agency of the Czech Republic, Subprograms 1 Technology leaders

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LM2023055, research and development project

Name: Česká národní infrastruktura pro biologická data

Investor: Ministry of Education, Youth and Sports of the CR, ELIXIR-CZ: Czech National Infrastructure for Biological Data

Citovat

VILÍM, Jan, Tereza GHAZALOVÁ, Eliška PETULOVÁ, Aneta HORACKOVA, Veronika STEPANKOVA, Radka CHALOUPKOVÁ, David BEDNÁŘ, Jiří DAMBORSKÝ and Zbyněk PROKOP. Computer-assisted stabilization of fibroblast growth factor FGF-18. Computational and Structural Biotechnology Journal. AMSTERDAM: Elsevier, 2023, vol. 21, October 2023, p. 5144-5152. ISSN 2001-0370. Available from: https://dx.doi.org/10.1016/j.csbj.2023.10.009.

@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 and Zbyněk PROKOP. Computer-assisted stabilization of fibroblast growth factor FGF-18. \textit{Computational and Structural Biotechnology Journal}. AMSTERDAM: Elsevier, 2023, vol.~21, October 2023, p.~5144-5152. ISSN~2001-0370. Available from: https://dx.doi.org/10.1016/j.csbj.2023.10.009.

Detailed Information on Publication Record