Dehydrophenylalanine (ΔPhe) as a β Breaker: Extended Structure Terminated by a ΔPhe‐Induced Turn in the Pentapeptide Boc‐Phe1‐Ala2‐Ile3‐ΔPhe4‐Ala5‐OMe

Abstract

Amyloid is a highly insoluble, aggregated state of certain polypeptide sequences associated with a range of debilitating diseases.A key step in amyloid formation is the transition of a protein from its native structure to a \beta-sheet arrangement; this suggests that the prevention of the ability of amyloidogenic proteins to adopt a \beta-sheet conformation would be useful as a way to impede the amyloid self-assembly process[1].The use of \beta-breaker residues is one approach for the development of peptide-based fibrillization-inhibiting drugs. Soto et al. demonstrated that the incorporation of \beta-sheet-breaker elements into short peptides composed of the recognition sequence of the amyloidogenic proteins inhibited amyloid formation. In this context, \beta-sheet-breaker residues, such as proline and a-aminoisobutyric acid (Aib), which is an unnatural amino acid residue, have been found to inhibit amyloid fibril formation.$^{[2a-d]}$