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Jul 23, 2019

Amyloid Inhibitory Peptides for Alzheimer’s Disease and Diabetes

Life Sciences, Neurology/CNS

  • macrocyclic peptides (MCIPs): novel class of nanomolar amyloid inhibitors of both Aβ40(42) and IAPP or of Aβ40(42) alone
  • candidates/leads for macrocyclic peptide‐based anti‐amyloid drugs
  • scaffolds for the design of small‐molecule peptidomimetics for targeting amyloidogenesis

Your contact

Dr. Katharina Stoiber

+49 (0) 89 5480177 - 40
Reference Number:


Amyloid self-assembly is linked to the pathogenesis of Alzheimer‘s disease (AD) and type 2 diabetes (T2D). Aβ40(42) is the main component of amyloid plaques in AD while islet amyloid polypeptide (IAPP) is the main component of pancreatic amyloid in T2D. Therefore blocking amyloidogenesis of the key amyloid polypeptides of AD and T2D is a promising therapeutic approach. However, so far the successful design of anti-amyloid compounds is hampered by several challenges including low proteolytic stability, low blood–brain barrier (BBB) permeability and high conformational flexibility. Thus, there is an urgent need to develop novel classes of amyloid inhibitors and exploit the therapeutic potential of blocking amyloidogenesis and related cell degeneration.


Here, macrocyclic peptides (MCIPs) were designed as a novel class of nanomolar amyloid inhibitors of both Aβ40(42) and IAPP or of Aβ40(42) alone.

Advantages and opportunities of the novel MCIPs:

  • MW < 2000
  • Easy and inexpensive synthetic production by solid phase synthesis methodology
  • Nanomolar inhibitors of amyloid self-assembly of both Aβ40(42) and IAPP
  • Nanomolar Aβ40(42)-selective inhibitors of amyloid self-assembly (in vitro & ex vivo)
  • High binding affinity
  • High solubility
  • High proteolytic stability in human plasma (shown in vitro)
  • Human BBB crossing ability (shown in a cell model)
  • High proteolytic resistance toward the brain protease neprilysin (shown in vitro)

Commercial Opportunities

Owing to their favorable properties, MCIPs are promising candidates/leads for macrocyclic peptide-based anti-amyloid drugs and scaffolds for the design of small-molecule peptidomimetics for targeting amyloidogenesis in AD or in both AD and T2D.

Development Status

Proof of concept of lead compound in vitro and in ex vivo electrophysiological studies in mouse brains.


  • Angew Chem Int Ed Engl. 2018 Jun 16. doi: 10.1002/anie.201802979.

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