Article ; Online: Hydrodynamic Control of Alzheimer Aβ Fibrillation with Glucosaminic Acid Containing Click-Cyclized β-Bodies.
Journal of the American Chemical Society
2023 Volume 146, Issue 4, Page(s) 2654–2662
Abstract: It is well established that the dynamic hydration shell plays a vital role in macromolecular functions such as protein-ligand, protein-protein, protein-DNA, and protein-lipid interactions. Here we investigate how the water modality affects conformational ...
| Abstract | It is well established that the dynamic hydration shell plays a vital role in macromolecular functions such as protein-ligand, protein-protein, protein-DNA, and protein-lipid interactions. Here we investigate how the water modality affects conformational changes, solubility, and motion of fibrillar proteins. The hypothesis is that the introduction of a poly hydroxyl amino acid would increase solvation of the fibril forming peptides, preventing their misfolding and aggregation. For the amyloid β (Aβ) peptide, which is considered to be connected with nervous system diseases, including dementia and cognitive decline in Alzheimer's disease, the formation of β-sheet fibrils always occurs with a conformational change and a decrease in the dynamic hydration shell around Aβ(1-42). We present novel cyclic d-amino acid peptides that effectively inhibit fibrillation through affecting the dynamic hydration shell of Aβ(1-42) in vitro. Using de novo design within the software Molecular Operating Environment (MOE), five different peptides that recognize Alzheimer's fibrils were designed and synthesized. Three of them were cyclic all-d-amino acid peptides incorporating the same polyhydroxy building block derived from d-glucosaminic acid ( |
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| MeSH term(s) | Humans ; Amyloid beta-Peptides/chemistry ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Hydrodynamics ; Amino Acids/chemistry ; Peptide Fragments/chemistry ; Glucosamine/analogs & derivatives |
| Chemical Substances | Amyloid beta-Peptides ; glucosaminic acid (6165-14-6) ; Amino Acids ; Peptide Fragments ; Glucosamine (N08U5BOQ1K) |
| Language | English |
| Publishing date | 2023-12-21 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 3155-0 |
| ISSN | 1520-5126 ; 0002-7863 |
| ISSN (online) | 1520-5126 |
| ISSN | 0002-7863 |
| DOI | 10.1021/jacs.3c12118 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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