α-sheet is a rare secondary structure of peptides. Unlike common peptides secondary structures，α-sheet exhibits polarity with orderly arranged inter-strand hydrogen bonds while maintaining an extended conformation of α-strand. Due to its unstable molecular arrangement，it has long been ignored as a temporary product during the protein folding process. With the advancement of crystallography and molecular dynamics simulation technologies，research on amyloid proteins causing various neurodegenerative diseases has found that α-sheet might be a critical intermediate in the formation of amyloid fibrils. Therefore，defining the formation cause and assembly mechanism of α-sheet can help to further understand the pathogenic principle of amyloid-related diseases and propose early diagnosis and targeted treatment strategies，as well as help to design self-assembly peptide biomaterials with various functions，such as piezoelectricity，biomimetic catalysis and drug delivery. In this review，we summarize recent progress of the peptides secondary structure，especially the rare secondary structures led by α-sheet，and focus on reviewing the self-assembly mechanism，regulatory mode and supramolecular structure of α-sheet peptides. In addition，the development potential of biomaterials based on self-assembly peptides has also been discussed.

Contents

1 Introduction

2 Peptide secondary structure in neurodegenerative diseases

2.1 β-sheet amyloid fibril

2.2 α-sheet intermediate

2.3 α to β conformational change

2.4 α-sheet peptide targeted therapy

3 Self-assembly peptides based on different chirality

4 Self-assembly peptides based on different secondary structure

4.1 β-sheet

4.2 α-helix

4.3 α-sheet

5 Conclusion and outlook