Oct 31, 2018

The Effect of Retro-inverse D-Amino Acid Aβ-peptides on Aβ- Fibril Formation

BioRxiv : the Preprint Server for Biology
Wenhui Xi, Ulrich H E Hansmann


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-Aβ40 and DRI-AAβ42 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-AAβ40 and DRI-AAβ42 peptides. We then explore the likelihood for cross fibrilization of AAβ L- and DRI-peptides by investigating how presence of DRI peptides alters elongation and stability of L- AAβ- fibrils. Our data suggest that full-length DRI-peptides may enhance the fibril formation and decrease the ratio of soluble toxic AAβ oligomers, pointing out a potential for D-amino-acid-based drug design targeting Alzheimers disease.

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Mentioned in this Paper

Molecular Dynamics
APP protein, human
Amino Acids, I.V. solution additive
Alzheimer's Disease
Proteolytic Enzyme
Toxic Effect
Amyloid Deposition

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