Synthesis and Mass Spectrometry Characterization of Anticancer Peptides to inhibit the Epidermal Growth Factor Receptor
Disciplines
Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
Cancer is a disease that dates to almost 3000 years ago when the first diagnosis took place. Ever since over one hundred types have evolved and continue to infest the systems of the human body.
The protein epidermal growth factor receptor (EGFR) contributes to cell division and sustainability in the body. Mutations of this protein in cancer cells can lead to an overactive production that results in the uncontrollable spread of cancer throughout the body. Although various small molecules drugs are developed to inhibit EGFR, very less studies are focused on peptide therapeutics. In this study, we have modelled two peptides, performed molecular docking with EGFR and then synthesized and characterize by liquid chromatography and mass spectrometry. GE11 is a dodecapeptide that can specifically bind itself to the EGF receptor and target the cancer cell. An additional analog of GE22, was screened as well in this study since previous research had shown it had a higher direct uptake in comparison to the primary peptide GE11. The leading ranked model of GE11 had a binding affinity value of -99.89 kcal/mol and GE11-22 additionally had the same binding affinity score. This is not a surprise since these peptides have a difference in just one amino acid. These leading peptides were then synthesized by standard Fmoc synthesis protocols using the CEM Liberty Blue peptide synthesizer. Analyzation and later characterization of these peptides were performed using mass spectrometry. The peaks shown for the GE11 peptide were at m/z 770.92 and 1540.67 which directly relate to the [M+2H]2+ and [M+H]+ charge states, respectively. GE11-22 peptide also showed similar charge states as the sequence are nearly same. In future, various cyclic and staple peptides will be synthesized and tested their performance by biological assay.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Synthesis and Mass Spectrometry Characterization of Anticancer Peptides to inhibit the Epidermal Growth Factor Receptor
Cancer is a disease that dates to almost 3000 years ago when the first diagnosis took place. Ever since over one hundred types have evolved and continue to infest the systems of the human body.
The protein epidermal growth factor receptor (EGFR) contributes to cell division and sustainability in the body. Mutations of this protein in cancer cells can lead to an overactive production that results in the uncontrollable spread of cancer throughout the body. Although various small molecules drugs are developed to inhibit EGFR, very less studies are focused on peptide therapeutics. In this study, we have modelled two peptides, performed molecular docking with EGFR and then synthesized and characterize by liquid chromatography and mass spectrometry. GE11 is a dodecapeptide that can specifically bind itself to the EGF receptor and target the cancer cell. An additional analog of GE22, was screened as well in this study since previous research had shown it had a higher direct uptake in comparison to the primary peptide GE11. The leading ranked model of GE11 had a binding affinity value of -99.89 kcal/mol and GE11-22 additionally had the same binding affinity score. This is not a surprise since these peptides have a difference in just one amino acid. These leading peptides were then synthesized by standard Fmoc synthesis protocols using the CEM Liberty Blue peptide synthesizer. Analyzation and later characterization of these peptides were performed using mass spectrometry. The peaks shown for the GE11 peptide were at m/z 770.92 and 1540.67 which directly relate to the [M+2H]2+ and [M+H]+ charge states, respectively. GE11-22 peptide also showed similar charge states as the sequence are nearly same. In future, various cyclic and staple peptides will be synthesized and tested their performance by biological assay.