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

Abstract

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.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

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

About this Paper

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Alzheimer's Disease: Genes&Microglia (Preprints)

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest preprints pertaining to this disease.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.