Developing Cationic Peptide Analogues for Alzheimer’s Treatment
Disciplines
Analytical Chemistry | Biochemistry
Abstract (300 words maximum)
Peptide therapeutics have gained traction over the past few years because they are a highly selective medication due to their targeted binding ability. They are better tolerated in the body because of their amino acid backbone. This is unlike small molecule drugs, which the body can develop a resistance to due to consistent use. The current understanding of Alzheimer’s is that it is caused by an overproduction of amyloid beta in the brain. Senile plaques begin to develop throughout, which leads to neurotoxicity. This increases the accumulation of amyloid beta, which then causes neurons to die off. With the current understanding of Alzheimer’s and its cause, the development of certain peptides has begun that will inhibit the production and presence of amyloid beta in the brain. In this project, we have developed two cationic peptide analogues incorporating basic amino acids in the N and C-terminal of the KLVFF motif. Previous studies showed that KLVFF can inhibit the amyloid beta fibril formation. In this study, two cationic peptide analogues including RGKLVFFGR (CP1) and RGKLVFFGK (CP2) are designed. We synthesized them by using the Liberty Blue peptide synthesizer with an automated Fmoc solid phase synthesis. It was cleaved using a 95% trifluoracetic acid mixture. The experimental mass of the synthesized peptides was measured by Orbitrap Exploris 240 mass spectrometry and confirmed with the theoretical mass. The binding affinity of the cationic peptides were measured against the amyloid beta using selected ion monitorial (SIM) based LCMS assay developed in our lab. The cationic peptide CP1 demonstrated a strong binding with a Kd value of 33 nM. Testing is still in progress for CP2 peptide. The preliminary result revealed that cationic peptides have potential to develop as effective therapeutics for Alzheimer's diseases.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Developing Cationic Peptide Analogues for Alzheimer’s Treatment
Peptide therapeutics have gained traction over the past few years because they are a highly selective medication due to their targeted binding ability. They are better tolerated in the body because of their amino acid backbone. This is unlike small molecule drugs, which the body can develop a resistance to due to consistent use. The current understanding of Alzheimer’s is that it is caused by an overproduction of amyloid beta in the brain. Senile plaques begin to develop throughout, which leads to neurotoxicity. This increases the accumulation of amyloid beta, which then causes neurons to die off. With the current understanding of Alzheimer’s and its cause, the development of certain peptides has begun that will inhibit the production and presence of amyloid beta in the brain. In this project, we have developed two cationic peptide analogues incorporating basic amino acids in the N and C-terminal of the KLVFF motif. Previous studies showed that KLVFF can inhibit the amyloid beta fibril formation. In this study, two cationic peptide analogues including RGKLVFFGR (CP1) and RGKLVFFGK (CP2) are designed. We synthesized them by using the Liberty Blue peptide synthesizer with an automated Fmoc solid phase synthesis. It was cleaved using a 95% trifluoracetic acid mixture. The experimental mass of the synthesized peptides was measured by Orbitrap Exploris 240 mass spectrometry and confirmed with the theoretical mass. The binding affinity of the cationic peptides were measured against the amyloid beta using selected ion monitorial (SIM) based LCMS assay developed in our lab. The cationic peptide CP1 demonstrated a strong binding with a Kd value of 33 nM. Testing is still in progress for CP2 peptide. The preliminary result revealed that cationic peptides have potential to develop as effective therapeutics for Alzheimer's diseases.