Coding

Part:BBa_K4165189

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


Amyloid beta peptide 9

This part encodes an Amyloid 𝛽 peptide (RFRK) which has the ability to bind to A𝛽 plaques inside the brain.

Usage and Biology

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.

A library of peptides was identified through phage display, it mostly contained 3 - 4 aa arginine-rich peptides that were tested for their inhibition activity of amyloid beta aggregates. The more the arginine residues in the peptide the higher its binding affinity to aggregates, which proposed this peptide as one of the stronger peptides.

This peptide contains both lysine and phenylalanine residues which enhances the peptide’s inhibition activity as of its increased cationicity and binding to the phenylalanine residue of Amyloid beta thus strengthening the interaction between them.


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

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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