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09:14
Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
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Cysteine-Selective Phosphonamidate Electrophiles for Modular Protein Bioconjugations
Marc-André Kasper1,2, Maria Glanz1,2, Andreas Stengl3
1Chemical Biology Department, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
Angewandte Chemie (International Ed. in English)
|March 5, 2019
Summary
A new Staudinger-phosphonite reaction (SPhR) creates stable protein conjugates. This method offers superior cysteine-selective reactivity and thiol adduct stability for advanced bioconjugation.
Area of Science:
- Bioconjugation Chemistry
- Protein Modification
- Organic Synthesis
Background:
- Existing protein modification techniques have limitations in stability and selectivity.
- Need for robust methods to create functional protein conjugates for various applications.
Purpose of the Study:
- To introduce a novel chemoselective reaction for protein modification.
- To develop a versatile tool for constructing stable functional protein conjugates.
Main Methods:
- Utilized a Staudinger-phosphonite reaction (SPhR) involving an azide-modified building block and an ethynylphosphonite.
- Generated an ethynylphosphonamidate intermediate.
- Demonstrated subsequent cysteine-selective bioconjugation with proteins and antibodies.
Main Results:
- Ethynylphosphonamidates exhibited excellent cysteine-selective reactivity.
- Achieved superior stability of thiol adducts compared to maleimide linkages.
- Successfully constructed stable functional protein conjugates.
Conclusions:
- The SPhR technique provides a powerful new method for protein modification.
- This approach enables the facile construction of highly stable protein conjugates.
- The developed method expands the repertoire of bioconjugation strategies.
Keywords:
bioconjugationbioorganic chemistrybioorthogonal chemistrycysteine-selective modificationprotein modificationMore Related Videos
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