Super-Chelators for Advanced Protein Labeling in Living Cells

Angew Chem Int Ed Engl. 2018 May 14;57(20):5620-5625. doi: 10.1002/anie.201800827. Epub 2018 Apr 14.

Abstract

Live-cell labeling, super-resolution microscopy, single-molecule applications, protein localization, or chemically induced assembly are emerging approaches, which require specific and very small interaction pairs. The minimal disturbance of protein function is essential to derive unbiased insights into cellular processes. Herein, we define a new class of hexavalent N-nitrilotriacetic acid (hexaNTA) chelators, displaying the highest affinity and stability of all NTA-based small interaction pairs described so far. Coupled to bright organic fluorophores with fine-tuned photophysical properties, the super-chelator probes were delivered into human cells by chemically gated nanopores. These super-chelators permit kinetic profiling, multiplexed labeling of His6 - and His12 -tagged proteins as well as single-molecule-based super-resolution imaging.

Keywords: cell delivery; live-cell imaging; metal-chelate complexes; protein labeling; super-resolution microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chelating Agents / chemistry*
  • Fluorescent Dyes / chemistry*
  • HeLa Cells
  • Humans
  • Kinetics
  • Molecular Structure
  • Nitrilotriacetic Acid / chemistry*
  • Optical Imaging
  • Proteins / analysis*

Substances

  • Chelating Agents
  • Fluorescent Dyes
  • Proteins
  • Nitrilotriacetic Acid