Protein quantification from complex protein mixtures using a proteomics methodology with single-cell resolution

Proc Natl Acad Sci U S A. 2001 May 8;98(10):5497-502. doi: 10.1073/pnas.101124598. Epub 2001 Apr 24.

Abstract

We have developed an extremely sensitive technique, termed immuno-detection amplified by T7 RNA polymerase (IDAT) that is capable of monitoring proteins, lipids, and metabolites and their modifications at the single-cell level. A double-stranded oligonucleotide containing the T7 promoter is conjugated to an antibody (Ab), and then T7 RNA polymerase is used to amplify RNA from the double-stranded oligonucleotides coupled to the Ab in the Ab-antigen complex. By using this technique, we are able to detect the p185(her2/neu) receptor from the crude lysate of T6-17 cells at 10(-13) dilution, which is 10(9)-fold more sensitive than the conventional ELISA method. Single-chain Fv fragments or complementarity determining region peptides of the Ab also can be substituted for the Ab in IDAT. In a modified protocol, the oligonucleotide has been coupled to an Ab against a common epitope to create a universal detector species. With the linear amplification ability of T7 RNA polymerase, IDAT represents a significant improvement over immuno-PCR in terms of sensitivity and has the potential to provide a robotic platform for proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Mice
  • Protein Processing, Post-Translational
  • Proteins / analysis*
  • Proteins / metabolism
  • Proteome*
  • Rats
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism

Substances

  • DNA Primers
  • Proteins
  • Proteome
  • Receptor, ErbB-2