ENGINEERING SELF-ASSEMBLY OF PEPTIDES BY AMPHIPHILIC 2D MOTIFS : α -TO-β TRANSITIONS OF PEPTIDES

A number of studies on disease-related proteins, such as those involved in Alzheimer’s or the prion diseases have led to improvements in our understanding of protein misfolding and transformation [1-11]. The studies have pointed out common and possible mechanisms for the formation of protein amyloid fibrils. Environments and mutations which might destabilize the native structures of proteins and facilitate the formation ofpartially unfolded intermediates have been demonstrated to be possible causes of the fibril formation of proteins [1-5], Such intermediates undergo peptide conformational transitions, which initiate protein aggregation and then fibril formation. Especially in the prion protein (PrP), a highly α-helicalstructure in the monomeric PrP is transformed to a βsheet conformation in aggregated protease-resistant PrPScC[6-8]. Similarly, β -amyloid peptides composed of 39-43 amino acid residues are also transformed to the amyloid form with a cross-β-sheet structure [911]. Although the mechanisms and intermediates of these amyloid formations have not yet been fully understood, it has been suggested that the aggregation process for the proteins from a less-β-structured monomer plays a key role in the conformational changes and the formation of amyloid with a higher β-sheet content [3,4]. In general, one cause of protein misfolding and transformation is thought to be the exposure of the hydrophobic region of proteins in an unstable form to water environments, and the formation of aggregates that follows. On the other hand, similar α→β transitions also occur through the correct-folding pathway from intermediates to native forms in proteins with a non-hierarchical folding mechanism such as β-lactoglobulin [12,13]. Moreover, the same peptide sequence named ‘chameleon’ adapted an α-helix or a β-strand at the different position in the protein, the B1