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Updated: Aug 26, 2025

Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition
Published on: December 23, 2016
Hydrophilic Azide-Containing Amino Acid to Enhance the Solubility of Peptides for SPAAC Reactions
Yixin Xie1, Tania L Lopez-Silva1, Joel P Schneider1
1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
Abstract:
We report a new positively charged azidoamino acid for strain-promoted azide-alkyne cycloaddition (SPAAC) applications that overcomes possible solubility limitations of commonly used azidolysine, especially in systems with numerous ligation sites. The residue is easily synthesized, is compatible with Fmoc-based solid-phase peptide synthesis employing a range of coupling conditions, and offers efficient second-order rate constants in SPAAC ligations employing DBCO (0.34 M-1 s-1) and BCN (0.28 M-1 s-1).
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