Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new-generation reagents were used in bioconjugation with an artificial retro-aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine-selective bioconjugation.
- Klíčová slova
- bioconjugation, cysteine, enzymes, fluorine, fluoroalkylation, hypervalent iodine,
- MeSH
- aminy chemie MeSH
- cystein chemie MeSH
- jod chemie MeSH
- karbodiimidy chemie MeSH
- lysin chemie MeSH
- proteiny chemie metabolismus MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- sulfhydrylové sloučeniny chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide MeSH Prohlížeč
- aminy MeSH
- cystein MeSH
- jod MeSH
- karbodiimidy MeSH
- lysin MeSH
- proteiny MeSH
- sulfhydrylové sloučeniny MeSH
A series of new hypervalent iodine reagents based on the 1,3-dihydro-3,3-dimethyl-1,2-benziodoxole and 1,2-benziodoxol-3-(1H)-one scaffolds, which contain a functionalized tetrafluoroethyl group, have been prepared, characterized, and used in synthetic applications. Their corresponding electrophilic fluoroalkylation reactions with various sulfur, oxygen, phosphorus, and carbon-centered nucleophiles afford products that feature a tetrafluoroethylene unit, which connects two functional moieties. A related λ(3) -iodane that contains a fluorophore was shown to react with a cysteine derivative under mild conditions to give a thiol-tagged product that is stable in the presence of excess thiol. Therefore, these new reagents show a significant potential for applications in chemical biology as tools for fast, irreversible, and selective thiol bioconjugation.
- Klíčová slova
- bioconjugation, fluorine, fluoroalkylation, hypervalent compounds, iodine, tetrafluoroethylene,
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
