Computer-assisted stabilization of fibroblast growth factor FGF-18

被引：2

作者：

Vilim, Jan ^{[1
,2
,3
]}

Ghazalova, Tereza ^{[3
]}

Petulova, Eliska ^{[3
]}

Horackova, Aneta ^{[3
]}

Stepankova, Veronika ^{[3
]}

Chaloupkova, Radka ^{[3
]}

Bednar, David ^{[1
,2
,4
]}

Damborsky, Jiri ^{[1
,2
,4
]}

Prokop, Zbynek ^{[1
,2
,4
]}

机构：

[1] Masaryk Univ, Fac Sci, Dept Expt Biol, Loschmidt Labs, Kamenice 5, Brno 62500, Czech Republic

[2] Masaryk Univ, Fac Sci, RECETOX, Kamenice 5, Brno 62500, Czech Republic

[3] Enantis Ltd, INBIT, Kamenice 34, Brno 62500, Czech Republic

[4] St Annes Univ Hosp Brno, Int Clin Res Ctr, Pekarska 53, Brno 656 91, Czech Republic

来源：

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL | 2023年 / 21卷

关键词：

Computer-assisted stabilization; Fibroblast growth factor; Thermostability; Resistance to; Protease; Improved yield; FGF-18; INTRAARTICULAR SPRIFERMIN; RECEPTOR SPECIFICITY; PROLIFERATION; PLACEBO; PROTEIN; FAMILY; FGF18;

D O I：

10.1016/j.csbj.2023.10.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5144 / 5152

页数：9

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