Comparative properties of Aβ1–42, Aβ11–42, and [Pyr11]Aβ11–42 generated from O-acyl isopeptides

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 5; pp. 1326 - 1329
• Main Authors: Sohma, Youhei, Yamasaki, Moe, Kawashima, Hiroyuki, Taniguchi, Atsuhiko, Yamashita, Masayuki, Akaji, Kenichi, Mukai, Hidehito, Kiso, Yoshiaki
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2013
• Subjects: Alzheimer Disease - metabolism; Amyloid beta-Peptides - chemistry; Circular Dichroism; Click peptide; Humans; Isopeptide; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Protein Structure, Secondary; Pyroglutamate; Aβ; Isopeptide; Pyroglutamate; Click peptide
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.12.082

The use of water-soluble O-acyl isopeptides enabled us to investigate the biochemical properties of Aβ11–42 species, by preparing highly concentrated stock solutions after a pretreatment. Aβ11–42 and [Pyr11]Aβ11–42 showed comparable aggregation capability and cytotoxicity, suggesting that the pyroglutamate modification at Glu11 does not have a crucial role in these events. However, given that Aβ11–42 is converted to [Pyr11]Aβ11–42 by a glutamyl cyclase in vivo, the potential aggregative and cytotoxic nature of [Pyr11]Aβ11–42 that was observed in the present study provides valuable insights into the pathological functions of pyroglutamate-modified Aβ species in Alzheimer’s disease.