Amyloid Protein-Induced Supramolecular Self-Assembly of Water-Soluble Platinum(II) Complexes: A Luminescence Assay for Amyloid Fibrillation Detection and Inhibitor Screening

J Am Chem Soc. 2019 Nov 20;141(46):18570-18577. doi: 10.1021/jacs.9b09515. Epub 2019 Nov 11.

Abstract

Amyloid fibrillation has been acknowledged as a hallmark of a number of neurodegenerative ailments such as Alzheimer's disease. Accordingly, efficient detection of amyloid fibrillation will allow for great advances in the field of biomedical applications as well as in achieving early medical diagnosis. In this work, a luminescence assay for the sensitive and specific detection of amyloid fibrillation was developed by using platinum(II) complexes as sensing platforms. Supramolecular self-assembly of platinum(II) complexes was induced upon addition of amyloid, leading to alterations in the spectroscopic and luminescence properties of the complexes. As compared to fluorescent dyes, luminescent platinum(II) complexes exhibit attractive large Stokes shifts, phosphorescence lifetimes in the microsecond to submicrosecond regime, and low-energy red emission after aggregation, which are advantageous to biological imaging. At the same time, the platinum(II) complex adopted herein was found to have high photostability, high selectivity and specificity, and low cytotoxicity. The proposed design is the very first approach to detect amyloid fibrillation through the supramolecular self-assembly of luminescent platinum(II) complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / analysis*
  • Amyloid / ultrastructure
  • Animals
  • Cattle
  • Coordination Complexes / chemistry*
  • Insulin / analysis*
  • Luminescent Agents / chemistry*
  • Luminescent Measurements
  • Microscopy, Confocal
  • Platinum / chemistry*
  • Solubility
  • Water / chemistry

Substances

  • Amyloid
  • Coordination Complexes
  • Insulin
  • Luminescent Agents
  • Water
  • Platinum