Dissociation of haemolytic and oligomer-preventing activities of gramicidin S derivatives targeting the amyloid-β N-terminus

Chem Commun (Camb). 2017 Dec 14;53(100):13340-13343. doi: 10.1039/c7cc08180d.

Abstract

The intrinsic haemolysis of an amyloid-β (Aβ) N-terminal targeting gramicidin S derivative was successfully dissociated from its Aβ oligomer-preventing activities via Ala-scanning-based regulation of molecular amphiphilicity. The representative analogue DGR-7 shows low toxicity but significant efficiency in preventing Aβ oligomers and reducing amyloid plaques in APP/PS1 transgenic AD mice.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Dose-Response Relationship, Drug
  • Gramicidin / adverse effects
  • Gramicidin / chemistry
  • Gramicidin / pharmacology*
  • Hemolysis / drug effects*
  • Mice
  • Mice, Transgenic
  • Molecular Conformation / drug effects
  • PC12 Cells
  • Plaque, Amyloid / drug therapy*
  • Plaque, Amyloid / metabolism
  • Rats

Substances

  • Amyloid beta-Peptides
  • Gramicidin