Azidophenylalanine
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| IUPAC name
(2S)-2-Amino-3-(4-azidophenyl)propanoic acid | |
Other names
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3D model (JSmol) |
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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 | |
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| 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).
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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]