Cyclic and dimeric fibroblast growth factor 2 variants with high biomedical potential.

Mateusz A Krzyscik, Łukasz Opaliński, Jakub Szymczyk, Jacek Otlewski

International journal of biological macromolecules 2022 Oct 01

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Fibroblast growth factor 2 (FGF2) is a pleiotropic protein engaged in the regulation of key cellular processes in a wide spectrum of cells. FGF2 is an important object of basic research as well as a molecule used in regenerative medicine, in vitro cell culture maintenance, and as an anticancer drug carrier. However, the unsatisfactory stability and pleiotropic activities of the wild-type FGF2 largely limit its use as a medical product. To overcome these limitations, we have designed a set of FGF2-based macromolecules via sortase A-mediated cyclization and oligomerization. We obtained heparin-switchable FGF2 variants with enhanced stability and improved ability to stimulate cell proliferation and migration. We have shown that stimulation of glucose uptake by adipocytes is modulated by the architecture of FGF2 oligomers. Moreover, we used hyper-stable FGF2 variants for the construction of highly effective drug carriers for selective killing of FGFR1-overproducing cancer cells. The strategy for FGF2 engineering presented in this work provides novel insights into the design of growth factor variants for regenerative and anti-cancer precise medicine. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Mateusz A Krzyscik, Łukasz Opaliński, Jakub Szymczyk, Jacek Otlewski. Cyclic and dimeric fibroblast growth factor 2 variants with high biomedical potential. International journal of biological macromolecules. 2022 Oct 01;218:243-258