Date of Graduation


Document Type


Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level



Chemistry & Biochemistry


Suresh Thallapuranam

Committee Member

Roger Koeppe

Second Committee Member

Frank Millett

Third Committee Member

Paul Adams

Fourth Committee Member

Wei Shi


Growth Factor, Stability, Wound Healing


Human acidic fibroblast growth factor (hFGF1) is a protein well known for its role in cell growth and differentiation. To elicit these cell-signaling processes, hFGF1 non-selectively binds to any one of the seven cell surface hFGF receptor isoforms. Due to its significant involvement in tissue repair activity, hFGF1 is a prime candidate for novel wound healing therapeutics. However, one drawback toward its use as a novel wound healing therapeutic is the poor inherent thermal stability of hFGF1, as it has been found to unfold near physiological temperature. The cause of this instability is strong electrostatic repulsion created by a dense cluster of positively charged amino acids near the c-terminus. This instability leads to proteolytic degradation of the unfolded protein, which severely limits the bioavailability of hFGF1. To counteract this instability, hFGF1 binds with high affinity to the heavily sulfated glycosaminoglycan, heparin, which eliminates the charge-charge repulsion via electrostatic interactions with the positively charged residues near the c-terminus in the region known as the heparin-binding pocket. However, recently several disadvantages have been acknowledged with the use of heparin in hFGF1 wound-healing therapeutics. Thus, to address these issues, we have genetically engineered several rationally designed point mutations within and near by the heparin-binding region of hFGF1 to modulate the heparin-binding affinity and to increase the thermal stability and cell proliferation activity of the protein. Study of each mutation is performed with biophysical experiments as well as molecular dynamics simulations (which are found as supplementary files).

SM1 wt-hFGF1.mp4 (5456 kB)
SM2 P135E.mp4 (8481 kB)
SM3 P135K.mp4 (8710 kB)
SM4 P135Q.mp4 (8691 kB)
SM5 P135ER136E.mp4 (8636 kB)
SM6 P135KR136E.mp4 (5031 kB)
SM7 wt-hFGF1.mpg (6236 kB)
SM8 D82R.mpg (9065 kB)
SM9 D84R.mpg (8217 kB)
SM10 D82RD84R.mpg (9299 kB)
SM11 D82N.mpg (8806 kB)
SM12 wt-hFGF1.mpg (25980 kB)
SM13 R136E5.mpg (32705 kB)

Included in

Biochemistry Commons