Home
Resources
Publications
Simultaneous Determination of Post-Translational Racemization and Isomerization of N-terminal amyloid-β in Alzheimer's Brain Tissues by Covalent Chiral Derivatized Ultraperformance Liquid Chromatography Tandem Mass Spectrometry

Simultaneous Determination of Post-Translational Racemization and Isomerization of N-terminal amyloid-β in Alzheimer's Brain Tissues by Covalent Chiral Derivatized Ultraperformance Liquid Chromatography Tandem Mass Spectrometry

Koichi Inoue, Daiju Hosaka, Nana Mochizuki, Hiroyasu Akatsu, Kaname Tsutsumiuchi, Yoshio Hashizume, Noriyuki Matsukawa, Takayuki Yamamoto, Toshimasa Toyo'oka

Anal Chem. 2014 Jan 7;86(1):797-804.

PMID: 24283798

Abstract:

Typical markers of protein aging are spontaneous post-translational modifications such as amino acid racemization (AAR) and amino acid isomerization (AAI) during the degradation of peptides. The post-translational AAR and AAI could significantly induce the density and localization of plaque deposition in brain tissues. Alzheimer's disease (AD) is reliably related to the formation and aggregation of amyloid-β peptide (Aβ) plaques in the human brain. No current analytical methods can simultaneously determine AAR and AAI during the degradation of Aβ from AD patients. We now report a covalent chiral derivatized ultraperformance liquid chromatography tandem mass spectrometry (CCD-UPLC-MS/MS) method for the determination of post-translational AAR and AAI of N-terminal Aβ (N-Aβ1-5) in human brain tissues. When subjected to tryptic N-Aβ1-5 from post-translationally modified natural Aβ in focal brain tissues by the CCD procedure, it was monitored at m/z 989.6→637.0/678.9 during electrospray collision-induced dissociation. These N-Aβ1-5 fragments with l-aspartic acid (l-Asp), d-Asp, l-isoAsp, and d-isoAsp could be separated using the UPLC system with a conventional reversed-phase column and mobile phase. The quantification of these peptides was determined using a stable isotope [(15)N]-labeled Aβ1-40 internal standard. The CCD-UPLC-MS/MS assay of potential N-Aβ1-5 allowed for the discovery of the present and ratio levels of these N-Aβ1-5 sequences with l-Asp, d-Asp, l-isoAsp, and d-isoAsp.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP202468277	L-Aspartic acid-13C4,15N		202468-27-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: