Part:BBa_K4165151

M4W39 Peptide

A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 of tau fibrils.

Usage and Biology

M4W39 is a peptide with amino acid sequence of DVWMINKKWK, it is acquired by mirror phage display 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 interaction between fibrils and consequently reduce the aggregates.

IC₅₀ = 2.9 μM

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]

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.

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.