An azide functionalized oligothiophene ligand--a versatile tool for multimodal detection of disease associated protein aggregates

Biosens Bioelectron. 2015 Jan 15:63:204-211. doi: 10.1016/j.bios.2014.07.042. Epub 2014 Jul 24.

Abstract

Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimer's and Parkinson's disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.

Keywords: Click chemistry; Fluorescence; Oligothiophene; Protein aggregates; Surface plasmon resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azides / chemistry*
  • Complex Mixtures
  • Equipment Design
  • Equipment Failure Analysis
  • Ligands
  • Protein Array Analysis / instrumentation*
  • Protein Interaction Mapping / instrumentation*
  • Spectrometry, Fluorescence / instrumentation
  • Surface Plasmon Resonance / instrumentation
  • Thiophenes / chemistry*

Substances

  • Azides
  • Complex Mixtures
  • Ligands
  • Thiophenes