Synthesis of Anticancer Peptide targeting the Epidermal Growth Factor Receptor
Abstract (300 words maximum)
Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein found within the cell interface belonging to a subfamily of receptor tyrosine kinases include EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). This protein is well known for its promotion and activation of key ligands that are responsible for cell growth, proliferation, and survival. When there is a genetic mutation it alters the structure of EGFR and causes uncontrolled cell growth, ultimately advancing to a tumor. Our aim is to design and develop an anticancer peptide therapeutic based on its ability to successfully bind to the EGFR membrane protein to prevent the progression of malignant and benign tumors. Based on the computational screening of 25 anti-cancer peptides, we synthesized two peptides during that resulted in having the strongest computational binding affinity to the EGFR protein. Solid phase peptide synthesis was applied, which began by swelling Rink Amide Resin. Cycles of deprotection and coupling were performed from the C’ terminus to the N’ terminus. After full peptide synthesis, we cleaved the peptide using TFA, removing the resin and sidechain protecting groups. Precipitation was then performed using cold ether. The purity of these peptides was tested using liquid chromatography and mass spectrometry. Our first peptide had a theoretical mass of 1172 Da. In mass spectrum, we obtained an experimental mass of 1171.67 Da. Our second peptide had a theoretical mass of 1383 Da while mass spectrometry of this peptide yielded in an experimental mass of 1382.77 Da. These findings indicate that both these peptides are successfully synthesized and pure. The inhibition efficiency for both these peptides will be evaluated via a biological assay which will be performed using cancer cell lines obtained observed using an anticancer in-vitro assay.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Synthesis of Anticancer Peptide targeting the Epidermal Growth Factor Receptor
Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein found within the cell interface belonging to a subfamily of receptor tyrosine kinases include EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). This protein is well known for its promotion and activation of key ligands that are responsible for cell growth, proliferation, and survival. When there is a genetic mutation it alters the structure of EGFR and causes uncontrolled cell growth, ultimately advancing to a tumor. Our aim is to design and develop an anticancer peptide therapeutic based on its ability to successfully bind to the EGFR membrane protein to prevent the progression of malignant and benign tumors. Based on the computational screening of 25 anti-cancer peptides, we synthesized two peptides during that resulted in having the strongest computational binding affinity to the EGFR protein. Solid phase peptide synthesis was applied, which began by swelling Rink Amide Resin. Cycles of deprotection and coupling were performed from the C’ terminus to the N’ terminus. After full peptide synthesis, we cleaved the peptide using TFA, removing the resin and sidechain protecting groups. Precipitation was then performed using cold ether. The purity of these peptides was tested using liquid chromatography and mass spectrometry. Our first peptide had a theoretical mass of 1172 Da. In mass spectrum, we obtained an experimental mass of 1171.67 Da. Our second peptide had a theoretical mass of 1383 Da while mass spectrometry of this peptide yielded in an experimental mass of 1382.77 Da. These findings indicate that both these peptides are successfully synthesized and pure. The inhibition efficiency for both these peptides will be evaluated via a biological assay which will be performed using cancer cell lines obtained observed using an anticancer in-vitro assay.