@article{1c30650e61eb4cb2a5f530fd2eda1e40,
title = "Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency",
abstract = "Fibroblast growth factor 21 (FGF21) has pharmaceutical potential against obesity-related metabolic disorders, including non-alcoholic fatty liver disease. Since thermal stability is a desirable factor for therapeutic proteins, we investigated the thermal behavior of human FGF21. FGF21 remained soluble after heating; thus, we examined its temperature-induced structural changes using circular dichroism (CD). FGF21 showed inter-convertible temperature-specific CD spectra. The CD spectrum at 100 °C returned to that at 20 °C when the heated FGF21 solution was cooled. Through loop swapping, the connecting loop between β10 and β12 in FGF21 was revealed to be associated with the unique thermal behavior of FGF21. According to surface plasmon resonance (SPR) experiments, in vitro cell-based assays, and model high-fat diet (HFD)-induced obesity studies, heated FGF21 maintained biological activities that were comparable to those of non-heated and commercial FGF21s. Based on sequence comparison and structural analysis, five point-mutations were introduced into FGF21. Compared with the wild type, the heated FGF21 variant displayed improved therapeutic potential in terms of body weight loss, the levels of hepatic triglycerides and lipids, and the degree of vacuolization of liver in HFD-fed mice.",
author = "Jung, {Ye Eun} and Lee, {Kyeong Won} and Cho, {Jae Hyun} and Bae, {Da Woon} and Jeong, {Bo Gyeong} and Jung, {Yeon Ju} and Park, {Soo Bong} and An, {Young Jun} and Kyungchan Kim and Lee, {Ga Seul} and Kang, {Lin Woo} and Moon, {Jeong Hee} and Lee, {Jung Hyun} and Kim, {Eun Kyoung} and Yim, {Hyung Soon} and Cha, {Sun Shin}",
note = "Funding Information: This work was supported by the project entitled “Development of Biomedical materials based on marine proteins” (the Ministry of Oceans and Fisheries, Republic of Korea) and the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. NRF2022R1A5A102641311). CD experiments were supported by Korea Basic Science Institute (National Research Facilities and Equipment Center) Grant funded by the Ministry of Education (2020R 1A 6C 101B194). We thank GENUV Inc. for allowing us to use a Biacore 8K system. Funding Information: This work was supported by the project entitled “Development of Biomedical materials based on marine proteins” (the Ministry of Oceans and Fisheries, Republic of Korea) and the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. NRF2022R1A5A102641311). CD experiments were supported by Korea Basic Science Institute (National Research Facilities and Equipment Center) Grant funded by the Ministry of Education (2020R 1A 6C 101B194). We thank GENUV Inc. for allowing us to use a Biacore 8K system. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41598-023-27717-x",
language = "English",
volume = "13",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}