Non-pretreated O-acyl isopeptide of amyloid β peptide 1–42 is monomeric with a random coil structure but starts to aggregate in a concentration-dependent manner

Abstract

An isopeptide of amyloid β peptide 1-42 (isoAβ42) was considered as a non-aggregative precursor molecule for the highly aggregative Aβ42. It has been applied to biological studies after several pretreatments. Here we report that isoAβ42 is monomeric with a random coil structure at 40 μM without any pretreatment. But we also found that isoAβ42 retains a slight aggregative nature, which is significantly weaker than that of the native Aβ42.

The Application of Isoacyl Structural Motifs in Prodrug Design and Peptide Chemistry

“…The same group also designed a switch peptide bearing a helix‐inducing component, which, once triggered, could reverse its secondary structure from a β sheet to an α helix and disrupt the preformed β‐sheet‐rich assemblies within amyloid fibrils (Scheme B) . Additional examples of applying the isoacyl motif to amyloid studies have also been reported by the group of Kiso and others . Overall, the O ‐acyl‐Ser/Thr isopeptide method has contributed significantly to the study of Aβ1–42 and peptides with similar properties, to understand the mechanisms of protein aggregation and potentially develop therapeutic strategies to prevent such processes.…”

“…[109] Additional examples of applying the isoacyl motif to amyloid studies have also been reported by the group of Kiso and others. [110][111][112][113][114] Overall, the O-acyl-Ser/Thr isopeptidem ethod has contributed significantly to the study of Ab1-42 and peptides with similarp roperties, to understand the mechanismso fp rotein aggregation and potentially develop therapeutic strategies to preventsuch processes.…”