Date of Graduation


Document Type


Degree Name

Bachelor of Science in Chemical Engineering

Degree Level



Chemical Engineering


Suresh Thallapuranam

Committee Member/Reader

Jamie Hestekin


The human acidic fibroblast growth factor (hFGF-1) is a protein that plays an important role in many body processes such as angiogenesis and tissue repair. As such, it has great potential for therapeutic application. However, hFGF-1 is relatively unstable in the body with a significant fraction being denatured at body temperature and pH. It contains a group of positively charged amino acids in close proximity that create an electrostatic strain on the molecule and can lead to denaturation and increased susceptibility to enzymatic digestion. Upon its release from the cell, hFGF-1 binds to the glycosaminoglycan heparin in the extracellular matrix. Heparin stabilizes hFGF-1 by binding to this group of positively charged amino acids, known as the heparin binding pocket. Heparin also mediates the binding of hFGF-1 to cell surface FGF Receptors (FGFRs). When activated by hFGF-1, these receptors propagate a signal downstream to initiate various pathways inside the cell. This study examines a mutation of hFGF-1 in which two negative charges are introduced into the heparin binding pocket. The introduction of these charges decreased the binding affinity of hFGF-1 for heparin by about 3-fold. This mutation also showed similar bioactivity compared to wild type hFGF-1 (wt-hFGF-1) both in the presence and absence of heparin. Overall, these results suggest that heparin binding affinity is not positively correlated with mitogenic activity. Additionally, it was shown that heparin binding is not necessary for activation of the tyrosine kinase cell surface receptor.


fibroblast growth factor, heparin, bioactivity