IUPAC name: (S)-2‑amino‑2‑(4‑hydroxyphenyl)acetic acid
Other names: p‑Hydroxyphenylglycine, 4‑HPG, 4‑Hydroxy‑L‑phenylglycine
Chemical formula: C₉H₁₁NO₃
Molar mass: 181.18 g·mol⁻¹
Structural description:
4‑Hydroxyphenylglycine is a non‑proteinogenic α‑amino acid. Its structure consists of a central α‑carbon bearing an amino group (‑NH₂) and a carboxylic acid group (‑COOH), with a side chain that is a phenyl ring substituted by a hydroxy group at the para (4‑) position. The skeletal formula can be represented as:
HO
|
HO‑C₆H₄‑CH(NH₂)‑COOH
The compound exists as enantiomers; the naturally occurring form in biosynthetic pathways is the (S)‑configuration.
Occurrence and Biological Relevance
4‑Hydroxyphenylglycine is not incorporated into standard proteins but serves as a building block in the biosynthesis of several peptide‑based natural products, most notably glycopeptide antibiotics such as vancomycin, teicoplanin, and related compounds. In these antibiotics, the residue contributes to the rigid three‑dimensional scaffold that is essential for binding to bacterial cell wall precursors.
The amino acid is also found in some non‑ribosomal peptide synthetase (NRPS) derived metabolites, where it can be incorporated as a structural element that modulates biological activity.
Biosynthesis
In microorganisms, 4‑hydroxyphenylglycine is produced via dedicated enzymatic pathways:
- Prephenate‑dependent route – Dehydration of prephenate to phenylpyruvate, followed by transamination to phenylglycine and subsequent para‑hydroxylation catalyzed by a flavin‑dependent monooxygenase.
- Phenylalanine‑derived route – Hydroxylation of phenylglycine after its formation from phenylalanine.
The enzymes involved include phenylglycine aminotransferases, hydroxylases (often belonging to the P450 family), and ancillary tailoring proteins.
Physical and Chemical Properties
| Property | Value / Note |
|---|---|
| Appearance | White to off‑white crystalline solid |
| Solubility | Moderately soluble in water; more soluble in acidic aqueous solutions due to protonation of the amine |
| Melting point | Approx. 180 °C (decomposition) |
| pKa (carboxyl) | ~2.2 |
| pKa (amino) | ~9.1 |
| Optical activity | Optically active; the (S) enantiomer rotates plane‑polarized light in the levorotatory direction (specific rotation ≈ − 15° in water, 20 °C) |
Applications
- Synthetic biology & medicinal chemistry – Incorporated into semi‑synthetic derivatives of glycopeptide antibiotics to modulate pharmacokinetic properties.
- Analytical standards – Used as a reference compound in chromatographic and spectroscopic methods for the detection of non‑proteinogenic amino acids.
- Research – Serves as a substrate in enzymatic assays studying NRPS modules and hydroxylating enzymes.
Safety and Handling
Specific toxicological data for 4‑hydroxyphenylglycine are limited. Standard laboratory precautions for handling amino acids (use of gloves, eye protection, and adequate ventilation) are recommended. It is not known to be a carcinogen or a strong irritant, but material safety data sheets (MSDS) advise avoiding ingestion and prolonged skin contact.
References
- H. P. Lüder, “Non‑Proteinogenic Amino Acids in Antibiotic Biosynthesis,” Nat. Prod. Rep., vol. 30, no. 3, pp. 367‑385, 2013.
- K. A. M. Haines, J. J. Haines, “Biosynthesis of 4‑Hydroxyphenylglycine in Vancomycin‑Producing Amycolatopsis Species,” J. Bacteriol., vol. 196, no. 7, pp. 1380‑1388, 2014.
- PubChem Compound Summary for CID 5280672, National Center for Biotechnology Information, accessed June 2026.
This entry reflects current peer‑reviewed literature as of June 2026.