Part:BBa_K4165012

Seed peptide (GGVVIA)

This part encodes Amyloid 𝛽 seed (37-42) which has the ability to bind to A𝛽 plaques inside the brain.

Usage and Biology

A short peptide derived from amyloid beta oligomers (A𝛽 37-42), which is proven to bind amyloid beta plaques inside the brain and stop plaque formation. This peptide showed no cytotoxicity when tested inside hippocampal cell lines, so it will be suitable to use as the targeting domain for A𝛽 plaques inside our system.

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 Characterization

Modeling

                                 Figure 1. RCSB model of seed peptide (37-42) visualized by Pymol. 

Docking

ΔG = -168.522

                      Figure 2. Docked structure of seed peptide against whole tau aggregates visualized by Pymol.

ΔG = -4.301

                      Figure 3. Docked structure of seed peptide against PHF of fibrils visualized by Pymol.

ΔG = -2.769

                     Figure 4. Docked structure of seed peptide against PHF* of fibrils visualized by Pymol.

ΔG = -44.19

                            Figure 5. Docked structure of seed peptide against amyloid beta.

Mathematical modeling

Transcription rate and translation rate under T7 promotor

the mathematical modeling was based on our code for the calculation of transcription and translation (you can find it in the code section) beside with the estimated results from the wet lab.

               Figure 6. this figure shows the results from the transcription and translation code showing the 
                    variation of mRNA and protein concentrations with time compared with the wet lab results.

References

1. Fradinger, E. A., Monien, B. H., Urbanc, B., Lomakin, A., Tan, M., Li, H., Spring, S. M., Condron, M. M., Cruz, L., Xie, W., Benedek, G. B., & Bitan, G. (2008). C-terminal peptides coassemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 105(37), 14175-14180. https://doi.org/10.1073/pnas.0807163105