Synthesis of Peptide Sequences Derived from Fibril-Forming Proteins
The pathogenesis of a large number of diseases, including Alzheimer’s Disease, Parkinson’s Disease, and Creutzfeldt–Jakob Disease (CJD), is associated with protein aggregation and the formation of amyloid, fibrillar deposits. Peptide fragments of amyloid-forming proteins have been found to form fibrils in their own right and have become important tools for unlocking the mechanism of amyloid fibril formation and the pathogenesis of amyloid diseases. The synthesis and purification of peptide sequences derived from amyloid fibril-forming proteins can be extremely challenging. The synthesis may not proceed well, generating a very low quality crude product which can be difficult to purify. Even clean crude peptides can be difficult to purify, as they are often insoluble or form fibrils rapidly in solution. This chapter presents methods to recognise and to overcome the difficulties associated with the synthesis, and purification of fibril-forming peptides, illustrating the points with three synthetic examples.
Key wordsSolid-phase peptide synthesis Fibril-forming peptide Microwave peptide synthesis Peptide HPLC purification ApoCII [56–76] Aβ[1–42] Prion protein
We thank Ms Keyla Perez for her advice with the Vydac C4 preparative column technology and peptide purifications performed at 60°C.
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