Difference between revisions of "Part:BBa K4165146"

 
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<partinfo>BBa_K4165146 short</partinfo>
 
<partinfo>BBa_K4165146 short</partinfo>
  
Tau binding peptide targeting the PHF* seed of Tau
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A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 of tau fibrils.
  
 
===Usage and Biology===
 
===Usage and Biology===
  
WINK is a peptide with amino acid sequence of DVQWINKKRK, 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. WINK can bind to PHF* in a mean that can disrupt the interface between each PHF* and consequently reduce the aggregates. Its IC<sub>50</sub> for inhibition of tau aggregates were 28.9 μM.  
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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.
  
 
<span class='h3bb'> <p style=" font-weight: bold; font-size:17px;"> Sequence and Features</p> </span>
 
<span class='h3bb'> <p style=" font-weight: bold; font-size:17px;"> Sequence and Features</p> </span>
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<p style=" font-weight: bold; font-size:14px;"> Modeling: </p>
 
<p style=" font-weight: bold; font-size:14px;"> Modeling: </p>
WINK is modeled by AlphaFold2, Apptest, ITASSER, and TrRosetta, best model obtained from ITASSER.
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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.
 
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/wink.png" style="margin-left:200px;" alt="" width="300" /></p>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/wink.png" style="margin-left:300px;" alt="" width="300" /></p>
 
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/wink-qa.png" style="margin-left:75px;" alt="" width="800" /></p>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/wink-qa.png" style="margin-left:50px;" alt="" width="800" /></p>
 
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<p style=" font-weight: bold; font-size:17px;"> IC<sub>50</sub> = 28.9 μM </p>
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===References===
 
===References===

Latest revision as of 13:52, 11 October 2022


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.