Synthesis of Peptides to Inhibit the Amyloid‑β Peptide Aggregation in Alzheimer Diseases
Disciplines
Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
Alzheimer’s disease is the most common form of dementia. It is an extremely prevalent neurological disease, effecting 60-70% of the more than 55 million people worldwide who have dementia according to the World Health Organization. The CDC reported that an estimated 6.5 million Americans were living with Alzheimer’s disease as of September 2022. By 2060, an amount estimated to increase to 14 million. Alzheimer diseases are related to the buildup of amyloid accumulations due to the aggregation of few specific peptides and proteins including Aβ peptides, α-Syn and Tau proteins. In the case of Alzheimer disease, clump peptide and protein undergo over production forming oligomers to large fibrils in neuron. This aggregation led to formation of Aβ peptides extracellular plaques whereas tau protein accumulates as intraneuronal inclusion bodies and form giant tangles. Fibril’s formation leads to synaptic dysfunction, neuron death, brain shrinkage and, ultimately, dementia. In this study, we plan to design therapeutics peptide to inhibit the aggregation and neurotoxicity imposed by Amyloid beta peptide.
In this study, we have synthesized two linear peptides (P1: KLVFF, and its reverse sequence P2: FFVFK) in a liberty blue peptide synthesizer using standard Fmoc-based synthesis protocols. The peptides then characterized using the Agilent 1290 UHPLC system equipped with a binary pump, a multisampler and a UV detector excitation at 214 nm. In addition, mass spectrometry experiment was performed using Thermo LTQ XL mass spectrometer equipped with a heated electrospray ionization (HESI) source. During HPLC experiment, both peptides eluted around 3.13 and 3.22 min and showed that the synthesized peptides are highly pure. The mass spectrometry peaks are detected at m/z 343.75 and 686.42 assigned to [M+2H]2+ and [M+H]+ ions, respectively which exactly matched with the theoretical values.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Synthesis of Peptides to Inhibit the Amyloid‑β Peptide Aggregation in Alzheimer Diseases
Alzheimer’s disease is the most common form of dementia. It is an extremely prevalent neurological disease, effecting 60-70% of the more than 55 million people worldwide who have dementia according to the World Health Organization. The CDC reported that an estimated 6.5 million Americans were living with Alzheimer’s disease as of September 2022. By 2060, an amount estimated to increase to 14 million. Alzheimer diseases are related to the buildup of amyloid accumulations due to the aggregation of few specific peptides and proteins including Aβ peptides, α-Syn and Tau proteins. In the case of Alzheimer disease, clump peptide and protein undergo over production forming oligomers to large fibrils in neuron. This aggregation led to formation of Aβ peptides extracellular plaques whereas tau protein accumulates as intraneuronal inclusion bodies and form giant tangles. Fibril’s formation leads to synaptic dysfunction, neuron death, brain shrinkage and, ultimately, dementia. In this study, we plan to design therapeutics peptide to inhibit the aggregation and neurotoxicity imposed by Amyloid beta peptide.
In this study, we have synthesized two linear peptides (P1: KLVFF, and its reverse sequence P2: FFVFK) in a liberty blue peptide synthesizer using standard Fmoc-based synthesis protocols. The peptides then characterized using the Agilent 1290 UHPLC system equipped with a binary pump, a multisampler and a UV detector excitation at 214 nm. In addition, mass spectrometry experiment was performed using Thermo LTQ XL mass spectrometer equipped with a heated electrospray ionization (HESI) source. During HPLC experiment, both peptides eluted around 3.13 and 3.22 min and showed that the synthesized peptides are highly pure. The mass spectrometry peaks are detected at m/z 343.75 and 686.42 assigned to [M+2H]2+ and [M+H]+ ions, respectively which exactly matched with the theoretical values.