Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition

Chem Asian J. 2011 Oct 4;6(10):2796-802. doi: 10.1002/asia.201100385. Epub 2011 Sep 8.

Abstract

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), the prototypical reaction of click chemistry, is accelerated by tris(triazolylmethyl)amine-based ligands. Herein, we compare two new ligands in this family--3-[4-({bis[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propanol (BTTP) and the corresponding sulfated ligand 3-[4-({bis[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propyl hydrogen sulfate (BTTPS)--for three bioconjugation applications: 1) labeling of alkyne-tagged glycoproteins in crude cell lysates, 2) labeling of alkyne- or azide-tagged glycoproteins on the surface of live mammalian cells, and 3) labeling of azides in surface proteins of live Escherichia coli. Although BTTPS exhibits faster kinetics than BTTP in accelerating the CuAAC reaction in in vitro kinetic measurements, its labeling efficiency is slightly lower than BTTP in modifying biomolecules with a significant amount of negative charges due to electrostatic repulsion. Nevertheless, the negative charge conferred by the sulfate at physiological conditions significantly reduced the cellular internalization of the coordinated copper(I), thus making BTTPS-Cu(I) a better choice for live-cell labeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemistry*
  • Catalysis
  • Click Chemistry
  • Copper / chemistry*
  • Cyclization
  • Escherichia coli / chemistry
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Flow Cytometry
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Kinetics
  • Ligands
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Staining and Labeling
  • Surface Properties

Substances

  • Alkynes
  • Azides
  • Escherichia coli Proteins
  • Ligands
  • Organometallic Compounds
  • Copper