Journal
JOURNAL OF CHEMICAL PHYSICS
Volume 150, Issue 9, Pages -Publisher
AMER INST PHYSICS
DOI: 10.1063/1.5082194
Keywords
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Funding
- National Science Foundation (NSF)
- National Institutes of Health (NIH) [GM120634]
- [MCB160005]
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Peptides build from D-amino acids resist enzymatic degradation. The resulting extended time of biological activity makes them prime candidates for the development of pharmaceuticals. Of special interest are D-retro-inverso (DRI) peptides where a reversed sequence of D-amino acids leads to molecules with almost the same structure, stability, and bioactivity as the parent L-peptides but increased resistance to proteolytic degradation. Here, we study the effect of DRI-A1340 and DRI-A1342 peptides on fibril formation. Using molecular dynamics simulations, we compare the stability of typical amyloid fibril models with such where the L-peptides are replaced by DRI-A1340 and DRI-A1342 peptides. We then explore the likelihood for cross fibrilization of Ap L- and DRI-peptides by investigating how the presence of DRI peptides alters the elongation and stability of L-A13-fibrils. Our data suggest that full-length DRI-peptides may enhance the fibril formation and decrease the ratio of soluble toxic Ap oligomers, pointing out potential for D-amino-acid-based drug design targeting Alzheimer's disease. Published under license by AIP Publishing.
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