Hydrophilic Azide-Containing Amino Acid to Enhance the Solubility of Peptides for SPAAC Reactions.

Org Lett

Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.

Published: October 2022

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 s) and BCN (0.28 M s).

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673676PMC
http://dx.doi.org/10.1021/acs.orglett.2c02906DOI Listing

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