Get access

Voltammetric Monitoring of Protein Aggregation from Solution Using Tris-(2,2′-Bipyridine) Osmium(II) Chloride Complex as an Electrocatalytic Mediator

Authors

  • Napoleon Tercero,

    Corresponding author
    1. National Institute of Standards and Technology, Biomolecular Measurement Division, 9600 Gudelsky Drive, Rockville, MD 20850, USA
    • National Institute of Standards and Technology, Biomolecular Measurement Division, 9600 Gudelsky Drive, Rockville, MD 20850, USA

    Search for more papers by this author
  • Joseph Kotarek

    Corresponding author
    1. National Institute of Standards and Technology, Biomolecular Measurement Division, 9600 Gudelsky Drive, Rockville, MD 20850, USA
    • National Institute of Standards and Technology, Biomolecular Measurement Division, 9600 Gudelsky Drive, Rockville, MD 20850, USA

    Search for more papers by this author
    • Both authors contributed equally to this work.


Abstract

The present work evaluates the feasibility of tracking protein aggregation voltammetrically by taking advantage of the intrinsic electroactivity of tyrosine residues. The electrocatalytic current due to the oxidation of tyrosine, mediated by tris-(2,2′-bipyridine)osmium(II) chloride, is used to report changes in protein aggregation state. We demonstrate, by the use of square wave voltammetry, that this system is able to differentiate between peptides containing equimolar tyrosine concentrations, and even detect tyrosine within large entities such as antibodies and insoluble amyloid fibrils. We also determine the aggregation time course of a model peptide, amyloid beta, detecting species with sizes from monomeric to insoluble aggregate. The method offers the prospect of monitoring biopharmaceutical aggregation and has potential to establish itself as a technique that is orthogonal to existing methods of aggregation detection.

Get access to the full text of this article

Ancillary