Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis.

The study of conformational transitions of peptides has obtained considerable attention recently because of their importance as a molecular key event in a variety of degenerative diseases. However, the study of peptide self-assembly into beta-sheets and amyloid beta (Abeta) fibrils is strongly hampered by their difficult synthetic access and low solubility. We have recently developed a new concept termed switch-peptides that allows the controlled onset of polypeptide folding and misfolding at physiologic conditions.

Switch-peptides: controlling self-assembly of amyloid beta-derived peptides in vitro by consecutive triggering of acyl migrations.

The sequential triggering (Soff --> Son) of O, N-acyl migrations (AcM) by chemical and enzymatic methods (Ti) in peptides containing structure-disrupting switch-elements, S (switch-peptides), offers a novel tool for studying in statu nascendi the onset and inhibition of polypeptide folding and self-assembly as a key process in degenerative diseases.