Part:BBa_K4165151

M4W39 Peptide

Tau binding peptide targeting the PHF seed of Tau

Usage and Biology

M4W39 is a peptide with amino acid sequence of DVWMINKKWK, it is designed to inhibit the fibrilization of tau which is one of the main drivers of Alzheimer’s disease and other dementia diseases. PHF* (VQIINK) is the site that derive tau aggregation. M4W39 can bind to PHF* in a mean that can disrupt the interface between each PHF* and consequently reduce the aggregates. Its IC₅₀ for inhibition of tau aggregates were 2.9 μM.

Dry Lab

Modeling

modeled by AlphaFold2, Apptest, ITASSER, best model obtained from AlphaFold2

                            Figure 1.: Predicted 3D structure of Synthetic peptide M4W39.

Table 1: Quality assessment parameters of M4W39 model.

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

References

1. Seidler, P. M., Boyer, D. R., Rodriguez, J. A., Sawaya, M. R., Cascio, D., Murray, K., ... & Eisenberg, D. S. (2018). Structure-based inhibitors of tau aggregation. Nature chemistry, 10(2), 170-176.