Developing Clinically Proven Peptide Analogues for Alzheimer’s Treatment
Disciplines
Biochemistry
Abstract (300 words maximum)
It has been theorized that the accumulation of beta-amyloid protein may be the cause of the progressive neurological disease known as Alzheimer's. The most commonly diagnosed form of dementia is Alzheimer's disease, affecting around six million Americans of all ages. Various theories surround the causes of this neurological disorder, resulting in different potential treatments. The beta-amyloid hypothesis suggests that the accumulation of beta-amyloid (Aβ) peptides leads to plaques forming in the brain, resulting in the death of neurons and other neural cells. This study has synthesized and tested several peptides for their binding ability to bind to the beta-amyloid peptide. The aim of this study is to develop potent analogues by modifying peptides that failed in clinical trials. The most qualified candidates have been selected for further synthesis and testing. A CEM Liberty Blue peptide synthesizer was used to perform solid-phase peptide synthesis protocols following standard Fmoc procedures and cleaved with 95% trifluoracetic acid. The peptide was precipitated using cold diethyl ether before being lyophilized. Peptide characterization was then performed using mass spectrometry. One of the peptides named “NAP” showed a strong peck at m/z 423.72, corresponding to its [M+2H]2+ charge state. The modified analogue named “NAPM” has a mass of m/z 1458.75 and showed a strong peak at m/z 729.92, corresponding to its [M+2H]2+ charge state. Both synthesized peptides were tested for their ability to bind with amyloid beta. The selected ion monitoring (SIM) based mass spectrometry assay result indicated strong binding (Kd =124 nM) between the amyloid beta and peptide inhibitor. Further research will be conducted to design more modified analogues and test their interaction with the amyloid beta employing hydrogen deuterium exchange mass spectrometry.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Developing Clinically Proven Peptide Analogues for Alzheimer’s Treatment
It has been theorized that the accumulation of beta-amyloid protein may be the cause of the progressive neurological disease known as Alzheimer's. The most commonly diagnosed form of dementia is Alzheimer's disease, affecting around six million Americans of all ages. Various theories surround the causes of this neurological disorder, resulting in different potential treatments. The beta-amyloid hypothesis suggests that the accumulation of beta-amyloid (Aβ) peptides leads to plaques forming in the brain, resulting in the death of neurons and other neural cells. This study has synthesized and tested several peptides for their binding ability to bind to the beta-amyloid peptide. The aim of this study is to develop potent analogues by modifying peptides that failed in clinical trials. The most qualified candidates have been selected for further synthesis and testing. A CEM Liberty Blue peptide synthesizer was used to perform solid-phase peptide synthesis protocols following standard Fmoc procedures and cleaved with 95% trifluoracetic acid. The peptide was precipitated using cold diethyl ether before being lyophilized. Peptide characterization was then performed using mass spectrometry. One of the peptides named “NAP” showed a strong peck at m/z 423.72, corresponding to its [M+2H]2+ charge state. The modified analogue named “NAPM” has a mass of m/z 1458.75 and showed a strong peak at m/z 729.92, corresponding to its [M+2H]2+ charge state. Both synthesized peptides were tested for their ability to bind with amyloid beta. The selected ion monitoring (SIM) based mass spectrometry assay result indicated strong binding (Kd =124 nM) between the amyloid beta and peptide inhibitor. Further research will be conducted to design more modified analogues and test their interaction with the amyloid beta employing hydrogen deuterium exchange mass spectrometry.