Coding

Part:BBa_K4165185

Designed by: Esraa Elmligy   Group: iGEM22_CU_Egypt   (2022-10-01)


Amyloid beta peptide 5 (R8-A𝛽 25-35)

This part encodes an Amyloid 𝛽 peptide which is the R8 peptide (BBa_K4165180) conjugated with Aß fragment (25-35). This peptide has the ability to bind to A𝛽 plaques inside the brain.

Usage and Biology

A bipartite peptide composed of two modules; a segment from the amyloid beta fibrils (Aß25-35) to allow peptide interaction with the fibrils, and a polyarginine peptide (R8) to act on inhibition of the self-aggregation of plaques.

Segments of amyloid beta fibrils are widely used as a recognition sequence for amyloid beta plaques inside the brain, they seemed to exert no cytotoxicity especially when bound to cationic arginine peptides.

Arginine (R) is a basic amino acid with the presence of a guanidino group at its aliphatic side chain. It is typically protonated at physiological pH where the guanidino group turns into a cationic guanidinium moiety that is highly stable and able to self-associate and cluster. These properties contribute to the intra- and intermolecular associations of arginine residues, as it provides a great capacity for electrostatic interactions (especially hydrogen-bonding) that results in a tendency to form stable clusters in solution.

Arginine has long been recognized as a chemical chaperone, with its ability to interact with and influence proteins in solution. In silico experiments have proved its ability to bind protein surfaces for a long time through its carboxyl and guanidinium groups, and form clusters through self-association with other arginine molecules. This has led to various in vitro experiments that proved the ability of arginine to suppress protein aggregations, which made it a very interesting candidate in the modulation of proteopathies correlated with Alzheimer’s disease.

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]


References

Cheng, Y., Chen, Z., Liao, T., Lin, C., Shen, H., & Wang, Y. et al. (2017). An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice. EMBO Molecular Medicine, 9(5), 703-715. doi: 10.15252/emmm.201606666

Mamsa, S. S., & Meloni, B. P. (2021). Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease. Frontiers in Molecular Neuroscience. https://doi.org/10.3389/fnmol.2021.759729

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