Amyloid Peptide Scaffolds Coordinate with Alzheimer’s Disease Drugs

Abstract

Functional amyloid materials can combine the selfassembly 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).

Co-Assembly of Cancer Drugs with Cyclo-HH Peptides: Insights from Simulations and Experiments

“…Self-assembled peptide materials possess a series of advantageous properties, particularly in their ability to form different types of nanostructures which can potentially serve as drug nanocarriers for drug release applications. , Therefore, a promising direction in cancer therapeutics is the design of new peptide materials that can be self-assembled for the encapsulation of cancer drugs . The intrinsic benefits of peptide self-assembled materials and the growing advances in computational and experimental approaches in the study and design of self-assembled systems − could serve as a means to design new classes of cancer drug delivery systems which may provide further alternatives to existing approaches. Additionally, they can serve as stepping stones for designing systems comprising peptide self-assembled materials, along with other materials for the delivery of cancer drugs.…”

Peptide Self-Assembled Nanocarriers for Cancer Drug Delivery

“…While self-assembled peptide nanocarriers for cancer drugs should not be considered a panacea to the challenges of cancer drug delivery, we consider that the intrinsic advantages of self-assembling peptide materials, along with the increasing progress in computational and experimental approaches for their study and design, could possibly lead to novel classes of systems that may provide additional alternatives to current approaches and/or provide a seed for novel multicomponent systems which may partly incorporate peptide self-assembled materials for cancer drug delivery. Importantly, due to the increasing advancement of computing capabilities and the development of novel computational study and design approaches in peptide self-assembly (e.g., refs − ), computations can play a key role in designing multicomponent systems and/or optimizing existing systems, based on feedback that can be provided by experimental in vitro/in vivo studies. Dr. Tamamis and Dr. Gazit envision that the design of novel self-assembling peptide cancer drug nanocarriers can be significantly enabled through integrated and synergistic experimental and computational approaches, with computational feedback provided to experiments and vice versa, ultimately leading to optimized systems and continuous improvment based on the design criteria and ultimately updating and refining the design criteria; such integrative and synergistic approaches could possibly provide means to jointly combat many issues to be addressed in the field, so that novel and improved cancer drug delivery systems, such as self-assembling peptide materials, can potentially and ultimately become translatable from the lab to the clinic.…”

CdTe QD-based inhibition and reactivation assay of acetylcholinesterase for the detection of organophosphorus pesticides

“…Mild inhibition has been shown to have therapeutic relevance in Alzheimer's disease (AD), myasthenia gravis, and glaucoma among others. 2,3 In contrast, the strong inhibition of AChE can lead to cholinergic poisoning. 4 To combat this, AChE reactivators have been developed to remove the offending AChE inhibitors, restoring acetylcholine levels to normal.…”