Date of Graduation
5-2022
Document Type
Thesis
Degree Name
Bachelor of Arts in Chemistry
Degree Level
Undergraduate
Department
Chemistry & Biochemistry
Advisor/Mentor
Thallapuranam, Suresh
Abstract
Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. FGF-1 non-selectively binds to all the known fibroblast growth factor receptors (FGFRs) and FGF-2 is strongly correlated with angiogenesis in a variety of bodily tissues, including muscle, adipose, bone, and tooth. The heterodimer also contains two mutations within the FGF-1 portion of the dimer, R136E and K126N. These mutations were induced to negate the overwhelming positive charge present in the heparin binding pocket (HBP) of FGF-1 and were found to increase the overall stability of the protein, increase cell proliferation activity, and decrease heparin binding affinity.10 The goal of this research project is to evaluate the dimer double mutant and compare its structure and function to that of the wild type FGF-1 and FGF-2 heterodimer. The heterodimer double mutant is found to have greater stability than the dimer wild type by having a greater trypsin resistance than the dimer wild type, as well as increased thermal stability both with and without the presence of stabilizing heparin. The continued investigation will provide valuable insight into the concept of FGF protein stability, and information regarding FGF dependence on heparin. This would enhance the knowledge pertinent to the possibility of novel wound healing agents comprised of FGFs in modern medicine.
Keywords
Protein Characterization, Protein Stability, Heterodimer, Wound Healing, Fibroblast Growth Factor
Citation
McClanahan, M. S. (2022). Hyper Stable Variants of FGF-1-FGF-2 Dimer. Chemistry & Biochemistry Undergraduate Honors Theses Retrieved from https://scholarworks.uark.edu/chbcuht/38
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Biological Factors Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical and Dental Materials Commons, Cell Biology Commons, Developmental Biology Commons, Medicinal Chemistry and Pharmaceutics Commons, Other Biochemistry, Biophysics, and Structural Biology Commons, Other Cell and Developmental Biology Commons