Azidophenylalanine
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| IUPAC name
(2S)-2-Amino-3-(4-azidophenyl)propanoic acid
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Other names
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3D model (JSmol)
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PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C9H10N4O2 | |
| Molar mass | 206.205 g·mol−1 |
| Appearance | Off-white solid |
| Hazards | |
| GHS labelling:[1] | |
| Warning | |
| H315, H319 | |
| P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P337+P317, P362+P364, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
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Azidophenylalanine (4-azido-L-phenylalanine) is an unnatural amino acid derivative of L-phenylalanine, featuring an azide group at the para position of the phenyl ring. It is a bioorthogonal click-chemistry reagent that can be genetically incorporated into proteins via expanded genetic code techniques for site-specific labeling and functionalization.[1] The compound serves as a vibrational reporter for local protein environments due to its azide group[2] and is used in photo-crosslinking for protein interaction studies.[3]
Chemical properties
Azidophenylalanine has the molecular formula C9H10N4O2 and a molecular weight of 206.20 g/mol.[4] Its IUPAC name is (2S)-2-amino-3-(4-azidophenyl)propanoic acid. It appears as an off-white solid and is soluble in water, DMSO, and DMF.[5]
As with many other azides, the isolated compound exhibits explosive properties.[5][6] It is light-sensitive and should be stored at -20 °C in the dark.
Synthesis
A chromatography-free synthesis of azidophenylalanine has been reported. It starts from L-phenylalanine and includes iodination to form 4-iodo-L-phenylalanine, followed by Boc protection, Cu(I)-catalyzed azidation using sodium azide (NaN3), deprotection with sulfuric acid, and purification by recrystallization.[5] This method avoids explosion risks associated with earlier approaches.
Research uses
As an analog of L-phenylalanine, azidophenylalanine is incorporated into proteins during translation in place of phenylalanine.[7] The azide group enables bioorthogonal reactions, such as copper-catalyzed or strain-promoted azide-alkyne cycloadditions, for protein modification.
Azidophenylalanine is employed in metabolic labeling to detect nascent protein synthesis as a non-radioactive alternative to traditional methods. It facilitates site-specific protein labeling for microscopic imaging, purification, and FRET studies. Applications include photochemical control of fluorescent proteins, synthesis of ligands for metal complexation in EPR/NMR, and probing protein dynamics during folding or catalysis. It is incorporated using orthogonal tRNA/synthetase pairs in systems like E. coli.[7]
References
- ^ Ma, Xiaofeng; Wei, Bing; Wang, Enlin (2022). "Efficient incorporation of p-azido-l-phenylalanine into the protein using organic solvents". Protein Expression and Purification. 200 106158. doi:10.1016/j.pep.2022.106158. PMID 36007861.
- ^ Löffler, Jan G.; Deniz, Erhan; Feid, Carolin; Franz, Valentin G.; Bredenbeck, Jens (2022). "Versatile Vibrational Energy Sensors for Proteins". Angewandte Chemie International Edition. 61 (21) e202200648. Bibcode:2022ACIE...61E0648L. doi:10.1002/anie.202200648. PMC 9401566. PMID 35226765.
- ^ Schwyzer, Robert; Caviezel, Mario (1971). "p -Azido-L-phenylalanine: A photo-affinity 'probe' related to tyrosine". Helvetica Chimica Acta. 54 (5): 1395–1400. doi:10.1002/hlca.19710540521. PMID 5121750.
- ^ CID 3080772 from PubChem
- ^ a b c Richardson, Mark B.; Brown, Derek B.; Vasquez, Carlos A.; Ziller, Joseph W.; Johnston, Kevin M.; Weiss, Gregory A. (2018). "Synthesis and Explosion Hazards of 4-Azido- l -phenylalanine". The Journal of Organic Chemistry. 83 (8): 4525–4536. doi:10.1021/acs.joc.8b00270. PMC 6008159. PMID 29577718.
- ^ Derek Lowe. "4-Azidophenylalanine: A Warning". In the Pipeline. Science. Retrieved January 25, 2026.
- ^ a b Chin, Jason W.; Santoro, Stephen W.; Martin, Andrew B.; King, David S.; Wang, Lei; Schultz, Peter G. (2002). "Addition of p -Azido-l-phenylalanine to the Genetic Code of Escherichia c oli". Journal of the American Chemical Society. 124 (31): 9026–9027. Bibcode:2002JAChS.124.9026C. doi:10.1021/ja027007w. PMID 12148987.