title: Copper-free click chemistry for highly luminescent quantum dot conjugates: application to in vivo metabolic imaging.
abstract: Quantum dots (QD) are inorganic nanocrystals with outstanding optical properties, specially suited for biological imaging applications. Their attachment to biomolecules in mild aqueous conditions for the design of bioconjugates is therefore highly desirable. 1,3-dipolar [3 + 2] cycloaddition between azides and terminal alkynes ("click chemistry") could represent an attractive QD functionalization method. Unfortunately, the use of the popular Cu(I)-catalyzed version of this reaction is not applicable for achieving this goal, since the presence of copper dramatically alters the luminescence properties of QD dispersions. We demonstrate here that copper-free click chemistry, between strained cyclooctyne functionalized QD and azido-biomolecules, leads to highly luminescent conjugates. In addition, we show that QD-cyclooctyne can be used at previously unreported low concentration (250 nM) for imaging the incorporation of azido-modified sialic acid in cell membrane glycoproteins.
authors.affiliation: CEA, LETI-MINATEC, Departement des Technologies pour la Biologie et la Sante, 17 rue des Martyrs, F-38054 Grenoble, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Bernardin
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazet
authors.forename: Laurent
authors.initials: L
authors.lastname: Guyon
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
authors.forename: Françoise
authors.initials: F
authors.lastname: Vinet
authors.forename: David
authors.initials: D
authors.lastname: Bonnaffé
authors.forename: Isabelle
authors.initials: I
authors.lastname: Texier
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D049449:Luminescence; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods*; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D045663:Quantum Dots
chemical_list: D000480:Alkynes; D001386:Azides; D008562:Membrane Glycoproteins; D003300:Copper; D019158:N-Acetylneuraminic Acid