Insight into the Working Mechanism of Quenchbody: Transition of the Dye around Antibody Variable Region That Fluoresces upon Antigen Binding

Bioconjug Chem. 2016 Oct 19;27(10):2248-2253. doi: 10.1021/acs.bioconjchem.6b00217. Epub 2016 Sep 26.

Abstract

Recently, we reported a novel immunoassay reagent Quenchbody (Q-body): a single chain antibody variable region (scFv) fragment labeled with fluorescent dye, whose fluorescence intensity increases when it binds to the antigen. Here we analyze its working mechanism by immuno- and fluorescence polarization (FP) assays. In an enzyme-linked immunosorbent assay, we found that in the presence of antigen osteocalcin peptide (BGP-C7), more TAMRA-labeled Q-bodies bound to anti-TAMRA antibody than in its absence. Moreover, we found that anti-BGP Q-body with the shortest linker that exhibits the largest antigen-dependency in fluorescence showed the highest binding signal. Similar results were obtained with anti-bisphenol A (BPA) Q-bodies, with inversed correlation with their linker lengths. In the FP assay, when the ATTO 520 labeled Q-body was added with antigen, the Brownian motion of the dye became more active, which resulted in reduced fluorescence anisotropy r. In other words, in the presence of antigen, 1/r showing that the dye mobility is larger than in the absence of its antigen. In addition, anti-BGP Q-body with the largest antigen-dependency in fluorescence showed the highest mobility. Overall, these results clearly suggest that the antigen-dependent fluorescence quenching and recovery of Q-body is caused by the movement of the dye within and around scFv, which moves out of scFv upon binding with its antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / chemistry
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Fluorescence Polarization / methods*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Methamphetamine / immunology
  • Osteocalcin / chemistry
  • Osteocalcin / metabolism
  • Phenols / chemistry
  • Rhodamines / chemistry
  • Rhodamines / metabolism
  • Single-Chain Antibodies / chemistry
  • Trichothecenes / immunology

Substances

  • 5-carboxytetramethylrhodamine succinimidyl ester
  • Benzhydryl Compounds
  • Fluorescent Dyes
  • Phenols
  • Rhodamines
  • Single-Chain Antibodies
  • Trichothecenes
  • Osteocalcin
  • Methamphetamine
  • deoxynivalenol
  • bisphenol A