title: Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition.
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.
authors: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461, USA.
authors: Wei
authors: W
authors: Wang
authors: Senglian
authors: S
authors: Hong
authors: Andrew
authors: A
authors: Tran
authors: Hao
authors: H
authors: Jiang
authors: Rebecca
authors: R
authors: Triano
authors: Yi
authors: Y
authors: Liu
authors: Xing
authors: X
authors: Chen
authors: Peng
authors: P
authors: Wu
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013194:Staining and Labeling; D013499:Surface Properties
chemical_list: D000480:Alkynes; D001386:Azides; D029968:Escherichia coli Proteins; D008024:Ligands; D009942:Organometallic Compounds; D003300:Copper