Přehled o publikaci
2024
Computer-aided engineering of stabilized fibroblast growth factor 21
DE LA BOURDONNAYE, Gabin; Tereza GHAZALOVÁ; Petr FOJTÍK; Katerina KUTALKOVA; David BEDNÁŘ et. al.Základní údaje
Originální název
Computer-aided engineering of stabilized fibroblast growth factor 21
Autoři
DE LA BOURDONNAYE, Gabin; Tereza GHAZALOVÁ; Petr FOJTÍK; Katerina KUTALKOVA; David BEDNÁŘ; Jiří DAMBORSKÝ; Vladimír ROTREKL; Veronika STEPANKOVA a Radka CHALOUPKOVÁ
Vydání
Computational and Structural Biotechnology Journal, Amsterdam, Elsevier, 2024, 2001-0370
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Organizace
Přírodovědecká fakulta – Masarykova univerzita – Repozitář
UT WoS
001187819700001
EID Scopus
2-s2.0-85184993217
Klíčová slova anglicky
Fibroblast growth factor 21; Protein engineering; Protein stabilization
Návaznosti
LM2023055, projekt VaV. LX22NPO5107, projekt VaV. RECETOX RI II, velká výzkumná infrastruktura.
Změněno: 15. 3. 2025 00:51, RNDr. Daniel Jakubík
Anotace
V originále
FGF21 is an endocrine signaling protein belonging to the family of fibroblast growth factors (FGFs). It has emerged as a molecule of interest for treating various metabolic diseases due to its role in regulating glucogenesis and ketogenesis in the liver. However, FGF21 is prone to heat, proteolytic, and acid-mediated degradation, and its low molecular weight makes it susceptible to kidney clearance, significantly reducing its therapeutic potential. Protein engineering studies addressing these challenges have generally shown that increasing the thermostability of FGF21 led to improved pharmacokinetics. Here, we describe the computer-aided design and experimental characterization of FGF21 variants with enhanced melting temperature up to 15 ◦C, uncompromised efficacy at activation of MAPK/ERK signaling in Hep G2 cell culture, and ability to stimulate proliferation of Hep G2 and NIH 3T3 fibroblasts cells comparable with FGF21-WT. We propose that stabilizing the FGF21 molecule by rational design should be combined with other reported stabilization strategies to maximize the pharmaceutical potential of FGF21.