Azidophenylalanine

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Azidophenylalanine
Azidophenylalanine.svg
Names
IUPAC name
(2S)-2-Amino-3-(4-azidophenyl)propanoic acid
Other names
  • 4-Azidophenylalanine
  • 4-Azido-L-phenylalanine
  • p-Azido-L-phenylalanine
  • AzF
  • 4AZP
Identifiers
3D model (JSmol)
PubChem CID
  • InChI=1S/C9H10N4O2/c10-8(9(14)15)5-6-1-3-7(4-2-6)12-13-11/h1-4,8H,5,10H2,(H,14,15)/t8-/m0/s1
    Key: NEMHIKRLROONTL-QMMMGPOBSA-N
  • C1=CC(=CC=C1C[C@@H](C(=O)O)N)N=[N+]=[N-]
Properties
C9H10N4O2
Molar mass 206.205 g·mol−1
AppearanceOff-white solid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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]

Contents

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

  1. ↑ 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.
  2. ↑ 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. PMID   35226765.
  3. ↑ 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.
  4. ↑ CID 3080772 from PubChem
  5. 1 2 3 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. PMID   29577718.
  6. ↑ Derek Lowe. "4-Azidophenylalanine: A Warning". In the Pipeline. Science. Retrieved January 25, 2026.
  7. 1 2 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 coli". Journal of the American Chemical Society. 124 (31): 9026–9027. Bibcode:2002JAChS.124.9026C. doi:10.1021/ja027007w. PMID   12148987.
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