Synthesis, Characterization, and In-Vitro Binding Affinity of Short Peptide Analogues Targeting the Amyloid Beta in Alzheimer Diseases
Disciplines
Analytical Chemistry | Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
Alzheimer's disease is the most common form of dementia that causes problems neurologically, basic memory functions eventually are damaged with Alzheimer's disease. Alzheimer's disease includes the symptoms of memory loss that intervenes with basic everyday tasks, the inability to form new memories, and repeating questions. It is estimated that over 50 million people suffer from this neurological condition and that number is soon to double in the next few years. Many factors can play into developing Alzheimer’s, such as the environment the individual is surrounded in, family genetics, and prior health issues. As many hypotheses are developing, Amyloid beta aggregation has been investigated and tested as a main therapeutic strategy for neurodegenerative disorders. The Aβ protein and its accumulation has led to the belief that it is the molecular driver of the disease of Alzheimer’s. In this research, three short peptide analogues including KVLFF, KLVFFA, and KLVFFAE were synthesized and characterized by mass spectrometry and tested the binding affinity against the amyloid-beta. Short peptides are easy to synthesis, characterize and cost-effective compared to large peptide inhibitors. These peptides were synthesized by the CEM Liberty Blue peptide synthesizer on a Rink-amide resin. The peptide-resin complex was dried with dichloromethane and subsequently cleavage was performed using 95% of trifluoroacetic acid, 2.5% of H2O, and 2.5% of Triisopropyl silane. The cleaved peptide was precipitated and lyophilized before characterizing them by mass spectrometry. KVLFF peptide showed two intense peaks at m/z 652.7 which correspond to [M+H]+ charge states. For two other analogues including KVLFFA and KLVFFAE demonstrated strong peaks at m/z 723.7 and 852.6 for [M+H]+ and at m/z 36.7 and 427.17 for [M+2H]2+ , respectively which agreed with the theoretical masses. The binding affinity of these peptides against the amyloid beta is under investigation, employing the selected ion monitoring based mass spectrometry assay.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Synthesis, Characterization, and In-Vitro Binding Affinity of Short Peptide Analogues Targeting the Amyloid Beta in Alzheimer Diseases
Alzheimer's disease is the most common form of dementia that causes problems neurologically, basic memory functions eventually are damaged with Alzheimer's disease. Alzheimer's disease includes the symptoms of memory loss that intervenes with basic everyday tasks, the inability to form new memories, and repeating questions. It is estimated that over 50 million people suffer from this neurological condition and that number is soon to double in the next few years. Many factors can play into developing Alzheimer’s, such as the environment the individual is surrounded in, family genetics, and prior health issues. As many hypotheses are developing, Amyloid beta aggregation has been investigated and tested as a main therapeutic strategy for neurodegenerative disorders. The Aβ protein and its accumulation has led to the belief that it is the molecular driver of the disease of Alzheimer’s. In this research, three short peptide analogues including KVLFF, KLVFFA, and KLVFFAE were synthesized and characterized by mass spectrometry and tested the binding affinity against the amyloid-beta. Short peptides are easy to synthesis, characterize and cost-effective compared to large peptide inhibitors. These peptides were synthesized by the CEM Liberty Blue peptide synthesizer on a Rink-amide resin. The peptide-resin complex was dried with dichloromethane and subsequently cleavage was performed using 95% of trifluoroacetic acid, 2.5% of H2O, and 2.5% of Triisopropyl silane. The cleaved peptide was precipitated and lyophilized before characterizing them by mass spectrometry. KVLFF peptide showed two intense peaks at m/z 652.7 which correspond to [M+H]+ charge states. For two other analogues including KVLFFA and KLVFFAE demonstrated strong peaks at m/z 723.7 and 852.6 for [M+H]+ and at m/z 36.7 and 427.17 for [M+2H]2+ , respectively which agreed with the theoretical masses. The binding affinity of these peptides against the amyloid beta is under investigation, employing the selected ion monitoring based mass spectrometry assay.