Peptide Therapeutics to Inhibit the Aggregation and Accumulation of Beta-Amyloid Plaques in Alzheimer’s Disease
Disciplines
Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
Alzheimer’s disease is a neurological disease that is theorized to be caused by the buildup of the beta-amyloid. Alzheimer’s disease is the most diagnosed neurological disease in the United States with 500,000 people being diagnosed a year. There are multiple theories as to why Alzheimer’s disease can occur in an individual. The most prominent one is the beta-amyloid hypothesis, which details that senile plaque formation, and the accumulation of beta-amyloid (Aβ) oligomer peptides is the major cause of Alzheimer’s disease. In this theory, small and soluble aggregates of beta-amyloid accumulate on the brain, disrupting communication between brain cells and eventually killing them. This is known to cause the major symptoms of Alzheimer’s, including memory loss, delusions, and the inability to form new memories. Peptide therapeutics can be used to delay effects of the disease and have been synthesized to bind to beta-amyloid fibrils and inhibit the aggregation and accumulation in the brain. In this study, multiple peptides were synthesized and tested upon their binding ability to the beta-amyloid peptide. The best candidates were chosen to be synthesized and tested. Standard Fmoc solid phase peptide synthesis protocols by CEM Liberty Blue peptide synthesizer were used to synthesize the peptides. Both peptide-resin complexes were cleavage using 95% trifluoracetic acid. Peptides were filtered and precipitated with cold diethyl ether. Peptide characterization was then conducted with Mass spectrometry. One of the peptides synthesized named “LAZ” shows two strong peaks at m/z 312 and 390 which correspond to the +5 and +4 charge states. The synthesized peptide was allowed to bind to the beta-amyloid 12-28 with varying concentrations. The high-resolution mass spectrometry studies showed that the peptide inhibitor strongly interacted with the beta-amyloid. Further research will be conducted on the interaction of these peptides with the beta-amyloid peptide employing native mass spectrometry techniques.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad Halim
Peptide Therapeutics to Inhibit the Aggregation and Accumulation of Beta-Amyloid Plaques in Alzheimer’s Disease
Alzheimer’s disease is a neurological disease that is theorized to be caused by the buildup of the beta-amyloid. Alzheimer’s disease is the most diagnosed neurological disease in the United States with 500,000 people being diagnosed a year. There are multiple theories as to why Alzheimer’s disease can occur in an individual. The most prominent one is the beta-amyloid hypothesis, which details that senile plaque formation, and the accumulation of beta-amyloid (Aβ) oligomer peptides is the major cause of Alzheimer’s disease. In this theory, small and soluble aggregates of beta-amyloid accumulate on the brain, disrupting communication between brain cells and eventually killing them. This is known to cause the major symptoms of Alzheimer’s, including memory loss, delusions, and the inability to form new memories. Peptide therapeutics can be used to delay effects of the disease and have been synthesized to bind to beta-amyloid fibrils and inhibit the aggregation and accumulation in the brain. In this study, multiple peptides were synthesized and tested upon their binding ability to the beta-amyloid peptide. The best candidates were chosen to be synthesized and tested. Standard Fmoc solid phase peptide synthesis protocols by CEM Liberty Blue peptide synthesizer were used to synthesize the peptides. Both peptide-resin complexes were cleavage using 95% trifluoracetic acid. Peptides were filtered and precipitated with cold diethyl ether. Peptide characterization was then conducted with Mass spectrometry. One of the peptides synthesized named “LAZ” shows two strong peaks at m/z 312 and 390 which correspond to the +5 and +4 charge states. The synthesized peptide was allowed to bind to the beta-amyloid 12-28 with varying concentrations. The high-resolution mass spectrometry studies showed that the peptide inhibitor strongly interacted with the beta-amyloid. Further research will be conducted on the interaction of these peptides with the beta-amyloid peptide employing native mass spectrometry techniques.