Sequential and parallel dual labeling of nanoparticles using click chemistry.

Autor: Zong H; Michigan Nanotechnology Institute for Medicine and Biological Sciences, United States. Electronic address: hzong@med.umich.edu., Goonewardena SN; Michigan Nanotechnology Institute for Medicine and Biological Sciences, United States; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, United States., Chang HN; Michigan Nanotechnology Institute for Medicine and Biological Sciences, United States., Otis JB; Michigan Nanotechnology Institute for Medicine and Biological Sciences, United States., Baker JR Jr; Michigan Nanotechnology Institute for Medicine and Biological Sciences, United States. Electronic address: jbakerjr@med.umich.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Nov 01; Vol. 22 (21), pp. 6288-96. Date of Electronic Publication: 2014 Jul 18.
DOI: 10.1016/j.bmc.2014.07.015
Abstrakt: Bioorthogonal 'click' reactions have recently emerged as promising tools for chemistry and biological applications. By using a combination of two different 'click' reactions, 'double-click' strategies have been developed to attach multiple labels onto biomacromolecules. These strategies require multi-step modifications of the biomacromolecules that can lead to heterogeneity in the final conjugates. Herein, we report the synthesis and characterization of a set of three trifunctional linkers. The linkers having alkyne and cyclooctyne moieties that are capable of participating in sequential copper(I)-catalyzed and copper-free cycloaddition reactions with azides. We have also prepared a linker comprised of an alkyne and a 1,2,4,5-terazine moiety that allows for simultaneous cycloaddition reactions with azides and trans-cyclooctenes, respectively. These linkers can be attached to synthetic or biological macromolecules to create a platform capable of sequential or parallel 'double-click' labeling in biological systems. We show this potential using a generation 5 (G5) polyamidoamine (PAMAM) dendrimer in combination with the clickable linkers. The dendrimers were successfully modified with these linkers and we demonstrate both sequential and parallel 'double-click' labeling with fluorescent reporters. We anticipate that these linkers will have a variety of application including molecular imaging and monitoring of macromolecule interactions in biological systems.
(Copyright © 2014. Published by Elsevier Ltd.)
Databáze: MEDLINE
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