ortho-Methoxyphenols as Convenient Oxidative Bioconjugation Reagents with Application to Site-Selective Heterobifunctional Cross-Linkers
| Autor: | Kareem M. El Muslemany, James I. MacDonald, Ioana L. Aanei, Adel M. ElSohly, Matthew B. Francis, Nina B. Hentzen |
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| Rok vydání: | 2017 |
| Předmět: |
Oxidative phosphorylation
010402 general chemistry Aminophenols 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Aniline Biomimetic Materials Site selective Organic chemistry Humans Bioconjugation Aniline Compounds Molecular Structure 010405 organic chemistry Periodate General Chemistry 0104 chemical sciences Cross-Linking Reagents Complex protein chemistry Reagent MCF-7 Cells Oxidative coupling of methane Oxidation-Reduction |
| Zdroj: | Journal of the American Chemical Society. 139(10) |
| ISSN: | 1520-5126 |
| Popis: | The synthesis of complex protein-based bioconjugates has been facilitated greatly by recent developments in chemoselective methods for biomolecular modification. The oxidative coupling of o-aminophenols or catechols with aniline functional groups is chemoselective, mild, and rapid; however, the oxidatively sensitive nature of the electron-rich aromatics and the paucity of commercial sources pose some obstacles to the general use of these reactive strategies. Herein, we identify o-methoxyphenols as air-stable, commercially available derivatives that undergo efficient oxidative couplings with anilines in the presence of periodate as oxidant. Mechanistic considerations informed the development of a preoxidation protocol that can greatly reduce the amount of periodate necessary for effective coupling. The stability and versatility of these reagents was demonstrated through the synthesis of complex protein-protein bioconjugates using a site-selective heterobifunctional cross-linker comprising both o-methoxyphenol and 2-pyridinecarboxaldehyde moieties. This compound was used to link epidermal growth factor to genome-free MS2 viral capsids, affording nanoscale delivery vectors that can target a variety of cancer cell types. |
| Databáze: | OpenAIRE |
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