Part:BBa_K4165146

WINK 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

WINK is a peptide with amino acid sequence of DVQWINKKRK, 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 derives tau aggregation. WINK can bind to PHF* in a way that can disrupt the interaction between fibrils and consequently reduce the aggregates, it is also believed to bind AB42 toxic fragments.

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:

WINK was modeled by AlphaFold2, Apptest, ITASSER, and TrRosetta, and best model obtained from ITASSER ranking 6 out of 6 according to our quality assessment code.

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

Table 1: Quality assessment parameters of WINK model.

IC₅₀ = 28.9 μM

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.