Installing Modified Phenylalanine to Improve Peptide Therapeutics for Alzheimer’s Diseases
Disciplines
Medicinal-Pharmaceutical Chemistry | Organic Chemistry
Abstract (300 words maximum)
Alzheimer’s disease is characterized by progressive neurodegenerative decline through the reduction in someone’s ability to recall information and regulate behavior. The pathogenesis of Alzheimer’s is correlated with a build-up of Amyloid- plaques within neurons. These plaques cause neurons to undergo oxidative stress and inflammation which in turn, causes the membrane to leak, leading to cell death. Since the issue is the buildup of amyloid-𝛽 plaques, the question is posed as to how the buildup of these could be prevented through the dissolution of conjoined amyloid-𝛽 plaques. The aim of this research is to test how modified methylated phenylalanine containing peptide interactions with amyloid-𝛽. In this research, methylated phenylalanine was utilized for its ability to stabilize peptide structure to improve binding affinity, proteases stability and fibril reduction. Four peptides were synthesized using solid phase peptide synthesis with Fmoc protecting the amino acid side chains. These four peptides were synthesized using amide resin and cleaved with the use of cocktail R due to the presence of multiple arginine amino acids. Cold ethyl ether added to the peptide solution allowed the peptide to precipitate. Acetic acid and water were added to the pellet, and frozen to be lyophilized. All four peptides were synthesized and identified by liquid chromatography coupled with mass spectrometry which showed the accurate molecular weights for each charged state (m/z). The preliminary results showed that methylated peptides strongly bind with amyloid beta and significantly reduced the amyloid-β fibril formation.
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Academic department under which the project should be listed
CSM – Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad Halim
Installing Modified Phenylalanine to Improve Peptide Therapeutics for Alzheimer’s Diseases
Alzheimer’s disease is characterized by progressive neurodegenerative decline through the reduction in someone’s ability to recall information and regulate behavior. The pathogenesis of Alzheimer’s is correlated with a build-up of Amyloid- plaques within neurons. These plaques cause neurons to undergo oxidative stress and inflammation which in turn, causes the membrane to leak, leading to cell death. Since the issue is the buildup of amyloid-𝛽 plaques, the question is posed as to how the buildup of these could be prevented through the dissolution of conjoined amyloid-𝛽 plaques. The aim of this research is to test how modified methylated phenylalanine containing peptide interactions with amyloid-𝛽. In this research, methylated phenylalanine was utilized for its ability to stabilize peptide structure to improve binding affinity, proteases stability and fibril reduction. Four peptides were synthesized using solid phase peptide synthesis with Fmoc protecting the amino acid side chains. These four peptides were synthesized using amide resin and cleaved with the use of cocktail R due to the presence of multiple arginine amino acids. Cold ethyl ether added to the peptide solution allowed the peptide to precipitate. Acetic acid and water were added to the pellet, and frozen to be lyophilized. All four peptides were synthesized and identified by liquid chromatography coupled with mass spectrometry which showed the accurate molecular weights for each charged state (m/z). The preliminary results showed that methylated peptides strongly bind with amyloid beta and significantly reduced the amyloid-β fibril formation.