Part:BBa_K4165141

MMD3 Peptide

A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 (BBa_K4165204) of tau fibrils.

Usage and Biology

MMD3 peptide (DPLKARHTSVWY) acquired by mirror image phage display, it is the D-enantiomeric peptide of MM3 (BBa_K4165154). It binds to ^275-VQIINK^-280 (PHF*) and ^306-VQIVYK^-311 (PHF) motifs of tau that are reported to drive tau paired helical filament aggregates. Thus, it inhibits formation of PHF6* and full‐length Tau aggregates, but not PHF driven aggregates, and prevents the formation of tau β‐sheet‐rich fibrils.

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

MMD3 was modeled by AlphaFold2, Apptest and ITASSER, and the best model was obtained from Apptest ranking 4 out of 6 according to our quality assessment code.

                                Figure 1.: Predicted 3D structure of Synthetic peptide MMD3.

Table 1: Quality assessment parameters of MMD3 model.

References

1. Malhis, M., Kaniyappan, S., Aillaud, I., Chandupatla, R. R., Ramirez, L. M., Zweckstetter, M., ... & Funke, S. A. (2021). Potent Tau Aggregation Inhibitor D‐Peptides Selected against Tau‐Repeat 2 Using Mirror Image Phage Display. ChemBioChem, 22(21), 3049-3059.