Developing Cyclic Peptide Therapeutics to Inhibit the Amyloid Beta in Alzheimer’s Disease
Disciplines
Biochemistry
Abstract (300 words maximum)
Alzheimer’s disease is a neurodegenerative disorder that affects nearly 6 million Americans primarily 65 and older and is the leading cause of dementia in the aging population. This disease is characterized by the progressive loss of cognitive function and ultimately leads to total loss of any memory and death within 10 years of diagnosis. The leading theory associated with the cause of Alzheimer’s is related to the accumulation of Amyloid Beta (AB) plaque. Peptide therapeutics has appeared to be a very promising field in terms of delaying and even eradicating the buildup of the Amyloid Beta in recent years. In this study, we synthesized linear (LP1) and cyclic peptide (CP1) using Fmoc based Solid-Phase peptide synthesis protocol. For cyclic peptide, two cysteine amino acids were installed into position 3 and 13. The cyclic peptide was synthesized by mixing the linear peptide with 10% DMSO and stirred for 48 hours at room temperature. The mass change of the cyclic peptide was monitored by mass spectrometry which demonstrated peaks at 332.6 and 415.5 corresponding to +5 and +4 charges, respectfully. The binding affinity of these peptides were measured against by the amyloid beta (AB) employing selected ion monitoring (SIM) based mass spectrometry assay. In this case, peptide concentration was fixed while AB concentration was varied from 1 to 100 micromolar. The binding affinity between peptides and AB was determined by the dissociation constant (Kd) which disclosed that cyclic peptide demonstrated a Kd value of 24 nanomolar (nM) while the linear peptide showed the Kd value of 268 nanomolar (nM). This study showed that cyclic peptides show promise to be an excellent therapeutic in inhibiting the amyloid beta.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Developing Cyclic Peptide Therapeutics to Inhibit the Amyloid Beta in Alzheimer’s Disease
Alzheimer’s disease is a neurodegenerative disorder that affects nearly 6 million Americans primarily 65 and older and is the leading cause of dementia in the aging population. This disease is characterized by the progressive loss of cognitive function and ultimately leads to total loss of any memory and death within 10 years of diagnosis. The leading theory associated with the cause of Alzheimer’s is related to the accumulation of Amyloid Beta (AB) plaque. Peptide therapeutics has appeared to be a very promising field in terms of delaying and even eradicating the buildup of the Amyloid Beta in recent years. In this study, we synthesized linear (LP1) and cyclic peptide (CP1) using Fmoc based Solid-Phase peptide synthesis protocol. For cyclic peptide, two cysteine amino acids were installed into position 3 and 13. The cyclic peptide was synthesized by mixing the linear peptide with 10% DMSO and stirred for 48 hours at room temperature. The mass change of the cyclic peptide was monitored by mass spectrometry which demonstrated peaks at 332.6 and 415.5 corresponding to +5 and +4 charges, respectfully. The binding affinity of these peptides were measured against by the amyloid beta (AB) employing selected ion monitoring (SIM) based mass spectrometry assay. In this case, peptide concentration was fixed while AB concentration was varied from 1 to 100 micromolar. The binding affinity between peptides and AB was determined by the dissociation constant (Kd) which disclosed that cyclic peptide demonstrated a Kd value of 24 nanomolar (nM) while the linear peptide showed the Kd value of 268 nanomolar (nM). This study showed that cyclic peptides show promise to be an excellent therapeutic in inhibiting the amyloid beta.