Amyloid Peptide Scaffolds Coordinate with Alzheimer's Disease Drugs.

Autor: Jonnalagadda SVR; Department of Chemical Engineering , Texas A&M University , College Station , Texas 77843 , United States., Gerace AJ; Department of Chemical Engineering , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States., Thai K; Department of Biology , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States., Johnson J; Department of Biology , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States., Tsimenidis K; Department of Chemistry , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States., Jakubowski JM; Department of Chemical Engineering , Texas A&M University , College Station , Texas 77843 , United States., Shen C; Department of Chemistry , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States., Henderson KJ; Department of Chemical Engineering , Texas A&M University , College Station , Texas 77843 , United States., Tamamis P; Department of Chemical Engineering , Texas A&M University , College Station , Texas 77843 , United States., Gkikas M; Department of Chemistry , University of Massachusetts Lowell , Lowell , Massachusetts 01854 , United States.
Jazyk: angličtina
Zdroj: The journal of physical chemistry. B [J Phys Chem B] 2020 Jan 23; Vol. 124 (3), pp. 487-503. Date of Electronic Publication: 2020 Jan 10.
DOI: 10.1021/acs.jpcb.9b10368
Abstrakt: 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).
Databáze: MEDLINE