Advantages:
- Developed sulfonyl-γ-AA peptide helical peptidomimetics that can prevent the formation of neurotoxic Aβ oligomerization.
- High Specificity: The lead sulfonyl-γ-AApeptide helical foldamer, Ab-6, exhibits precise targeting to the central region of Aβ42 and induces α-helix conformation in Aβ.
- Sequence-Specific Inhibition: Ab-6 demonstrates sequence-specific inhibition of Aβ oligomerization, providing a targeted approach at the molecular level.
- The technology not only inhibits Aβ aggregation but also rescues neuroblastoma cells, protecting mitochondrial function from Aβ42-induced damage.
Summary:
This invention presents sulfonyl-γ-AApeptide helices specifically designed to target the cationic, hydrophobic, and anionic domains of the amyloid-beta (Aβ) protein implicated in Alzheimer's Disease. These peptides are novel due to their well-defined helical structures, resistance to proteolysis, and ability to induce and stabilize the α-helical conformation of Aβ₄₂, preventing the formation of neurotoxic β-sheet aggregates. The lead molecule, Ab-6 demonstrates strong binding affinity to Aβ₄₀ and effectively inhibits both spontaneous and seed-induced fibrillation of Aβ₄₂ .Ab-6 protects neuronal cells from Aβ₄₂-induced toxicity, and co-localizes with Aβ₄₂ in mitochondria, suggesting a protective effect on mitochondrial function.
In summary, the unique molecular design of sulfonyl-γ-AApeptides helical peptidomimetics leads to a higher efficacy in the sequence-specific and dose-dependent prevention, and even reversal, of Aβ oligomerization and fibrillation. This technology presents a compelling alternative within the AD therapeutics field and could be applied to combat various amyloid diseases.
Figure 1. The structure of sulfonyl-γ-AApeptides and their use as ligands to stabilize helical structure of Aβ peptide. a Chemical structure of sulfonyl-γ-AApeptide. ‘a’ and ‘b’ represent the chiral side chain and sulfono side chain, respectively. b and c are the side view and top view of sulfonyl-γ-AApeptide foldamer. d The schematic illustration of helical Aβ peptide stabilized by ligands.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development