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

Taku Yoshiya; Takahiro Maruno; Tsuyoshi Uemura; Shigeru Kubo; Yoshiaki Kiso; Youhei Sohma; Kumiko Yoshizawa-Kumagaye; Yuji Kobayashi; Yuji Nishiuchi

doi:10.1016/j.bmcl.2014.06.052

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

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3861-4. doi: 10.1016/j.bmcl.2014.06.052. Epub 2014 Jun 25.

Authors

Taku Yoshiya¹, Takahiro Maruno², Tsuyoshi Uemura³, Shigeru Kubo³, Yoshiaki Kiso⁴, Youhei Sohma⁵, Kumiko Yoshizawa-Kumagaye³, Yuji Kobayashi², Yuji Nishiuchi⁶

Affiliations

¹ Peptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-Shi, Osaka 567-0085, Japan. Electronic address: t.yoshiya@peptide.co.jp.
² Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan.
³ Peptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-Shi, Osaka 567-0085, Japan.
⁴ Laboratory of Peptide Science, Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan.
⁵ Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
⁶ Peptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-Shi, Osaka 567-0085, Japan; Graduate School of Science, Osaka University, Osaka 560-0043, Japan.

PMID: 25017031
DOI: 10.1016/j.bmcl.2014.06.052

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.

Keywords: Alzheimer’s disease; Amyloid β peptide; Analytical ultracentrifugation; O-Acyl isopeptide; O-to-N intramolecular acyl migration.

MeSH terms

Amyloid beta-Peptides / chemistry*
Peptide Fragments / chemistry*
Protein Conformation

Substances

Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)