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Sulfated Ligands for the Copper(I)‐Catalyzed Azide–Alkyne Cycloaddition
Author(s) -
Wang Wei,
Hong Senglian,
Tran Andrew,
Jiang Hao,
Triano Rebecca,
Liu Yi,
Chen Xing,
Wu Peng
Publication year - 2011
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201100385
Subject(s) - bioconjugation , chemistry , cycloaddition , click chemistry , alkyne , azide , ligand (biochemistry) , amine gas treating , combinatorial chemistry , triazole , catalysis , medicinal chemistry , stereochemistry , organic chemistry , biochemistry , receptor
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‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]amino}methyl)‐1 H ‐1,2,3‐triazol‐1‐yl]propanol (BTTP) and the corresponding sulfated ligand 3‐[4‐({bis[(1‐ tert ‐butyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]amino}methyl)‐1 H ‐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.