FGF-1: from biology through engineering to potential medical applications.
Human fibroblast growth factor 1 (FGF-1) is one of the best characterized members of the FGF superfamily. FGF-1 is a powerful mitogen exhibiting strong action on numerous different cell types. It plays a role in various stages of development and morphogenesis, as well as in angiogenesis and wound healing processes. Engineering of FGFs can bring many advantages. Design and construction of different mutants can contribute to a better understanding of the mechanism of action of protein growth factors. Moreover, application of FGFs as recombinant polypeptides in the treatment of wound and fracture healing, cardiovascular diseases and neurodegenerative diseases seems to be a rational medical approach. However, low thermal stability and high sensitivity to proteases limit the potential pharmaceutical use of wild-type FGFs. Thus, advanced protein design techniques and recombinant protein production can help to obtain new variants of FGFs with radically increased thermodynamic stability, prolonged half-life and improved proteolytic resistance. Such studies can provide a good starting point to convert short-lived and/or sensitive growth factors to effective therapeutic proteins.
Zakrzewska
Malgorzata
M
Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland. ewa@protein.pl
Marcinkowska
Ewa
E
Wiedlocha
Antoni
A
D015510:Clinical Medicine / Q000379:methods*; D004358:Drug Therapy; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015202:Protein Engineering; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1