Detoxification depot for beta-amyloid peptides.
Alzheimer's Disease (AD) is caused by the deposition of insoluble and toxic amyloid peptides (Abeta) in the brain leading to memory loss and other associated neurodegenerative symptoms. To date there is limited treatment options and strategies for treating AD. Studies have shown that clearance of the amyloid plaques from the brain and thus from the blood could be effective in stopping and or delaying the progression of the disease. Small peptides derived from the Abeta-42 sequence, in particular KLVFF, have shown to be effective binders of Abeta peptides and thus could be useful in delaying progression of the disease. We have taken advantage of this property by generating the retro-inverso (RI) version of this peptide, ffvlk, in different formats. We are presenting a new detox gel system using poly ethylene glycol (PEG), polymerized and cross linked with the RI peptides. We hypothesize that detox gel incorporating RI peptides will act like a 'sink' to capture the Abeta peptides from the surrounding environment. We tested these detox gels for their ability to capture biotinylated Abeta-42 peptides in vitro. The results showed that the detox gels bound Abeta-42 peptides effectively and irreversibly. Gels incorporating the tetramer RI peptide exhibited maximum binding capacity. The detox gel could be a potential candidate for treatment strategies to deplete the brain of toxic amyloid peptides.
Sundaram
Ranjini K
RK
Recombinant Technologies LLC, Cheshire, CT 06410, USA.
Kasinathan
Chinnaswamy
C
Stein
Stanley
S
Sundaram
Pazhani
P
D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D000596:Amino Acids / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000302:isolation & purification* / Q000378:metabolism; D019921:Biotinylation; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D016060:Sorption Detoxification / Q000379:methods*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D004343:Drug Implants; D020100:Hydrogels; D009842:Oligopeptides; D010446:Peptide Fragments; D011092:Polyethylene Glycols