Scientists in Germany have worked on optimising compounds that reduce the formation of amyloid β-peptides, which play a crucial role in the development and progression of Alzheimer’s disease. The team varied the membrane anchor, spacer and pharmacophore building blocks on BACE1 inhibitors to make tripartite structures (assembled by covalent coupling of BACE1 inhibitors with membrane anchors via suitable spacers).
Several BACE1 inhibitors have already been reported, but here, the team has shown that the cellular activity of small-molecule BACE1 inhibitors can be significantly increased by membrane targeting via a spacer with a raftophilic membrane anchor.
Optimisation of BACE1 Inhibition of Tripartite Structures by Modification of Membrane Anchor, Spacer and Pharmacophore – Development of Potential Agents for the Treatment of Alzheimer’s Disease
Hans-Joachim Knölker
DOI: 10.1039/C2OB26103K
