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.

Základní údaje

Originální název

Computer-assisted stabilization of fibroblast growth factor FGF-18

Autoři

VILÍM, Jan; Tereza GHAZALOVÁ; Eliška PETULOVÁ; Aneta HORACKOVA; Veronika STEPANKOVA; Radka CHALOUPKOVÁ; David BEDNÁŘ; Jiří DAMBORSKÝ a Zbyněk PROKOP

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.500

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00133177

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

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

Štítky

14314010, 143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 4. 3. 2026 08:45, Mgr. Michaela Hylsová, Ph.D.

Anotace

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.

Návaznosti

EF18_053/0016952, projekt VaV

Název: Postdoc2MUNI

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LM2023055, projekt VaV

Název: Česká národní infrastruktura pro biologická data

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, ELIXIR-CZ: Česká národní infrastruktura pro biologická data

Citovat

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. Computational and Structural Biotechnology Journal. AMSTERDAM: Elsevier, 2023, roč. 21, October 2023, s. 5144-5152. ISSN 2001-0370. Dostupné z: https://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 = {https://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://doi.org/10.1016/j.csbj.2023.10.009.

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