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First Immunoassay for Measuring Isoaspartate in Human Serum Albumin

Jijing Wang, Susanna L. Lundström, Sven Seelow, Sergey Rodin, Zhaowei Meng, Juan Astorga‐Wells, Qinyu Jia, Roman A. Zubarev

2021Molecules13 citationsDOIOpen Access PDF

Abstract

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins mostly as a result of spontaneous deamidation of asparaginyl residues. An association has been found between isoAsp in human serum albumin (HSA) and Alzheimer's disease (AD). Here we report on a novel monoclonal antibody (mAb) 1A3 with excellent specificity to isoAsp in the functionally important domain of HSA. Based on 1A3 mAb, an indirect enzyme-linked immunosorbent assay (ELISA) was developed, and the isoAsp occupancy in 100 healthy plasma samples was quantified for the first time, providing the average value of (0.74 ± 0.13)%. These results suggest potential of isoAsp measurements for supplementary AD diagnostics as well as for assessing the freshness of stored donor blood and its suitability for transfusion.

Topics & Concepts

DeamidationImmunoassayMonoclonal antibodyChemistryHuman serum albuminAmino acid residueResidue (chemistry)BiochemistryChromatographyAntibodyMedicineEnzymePeptide sequenceImmunologyGeneProtein purification and stabilityProtein Interaction Studies and Fluorescence AnalysisMonoclonal and Polyclonal Antibodies Research