Amyloid Peptide Scaffolds Coordinate with Alzheimer’s Disease Drugs
2020
Functional
amyloid materials can combine the self-assembly of peptide
scaffolds into amyloid fibrils with binding capacities for ions or
compounds of pharmaceutical interest, endowed by mutable non-β-sheet-forming
residues at the termini. Herein, we report the first to our knowledge
amyloid materials, encompassing a GAIIG amyloidogenic core, which
bind to Alzheimer’s disease (AD) drugs, by mimicking the mechanism
by which the same AD drugs bind to enzymes according to experimentally
resolved structures, including the target enzyme acetylcholinesterase
(AChE). The computationally designed amyloid scaffolds are experimentally
shown to coordinate with AD drugs, using two techniques, both in dilute
solutions and at higher peptide concentrations, with a higher binding
capacity for donepezil and tacrine compared to that for memantine
and galantamine. The binding for some of the AD drugs is strong and
stable even after extensive subsequent aqueous washings, denoting
high capturing efficiency by the designed biomaterials, even after
incubation under physiological conditions. Our findings constitute
starting points to design novel drug delivery carriers binding to
one or combinations of AD drugs (e.g., NMDA and cholinesterase inhibitors).
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
89
References
2
Citations
NaN
KQI