Tyrosine (Tyr, Y)
Tyrosine is an aromatic amino acid with a phenol side chain. It contributes UV absorbance, hydrogen bonding and phosphorylation sites, and is the N-terminal residue of many receptor-active peptides.
Structure and properties
Tyrosine carries a phenol, a benzene ring bearing a hydroxyl group. The ring gives aromatic stacking and hydrophobic contact, while the hydroxyl adds hydrogen bonding, so tyrosine is amphipathic and common at protein interfaces and membrane boundaries. The phenol is weakly acidic and remains neutral at physiological pH. Tyrosine absorbs ultraviolet light and fluoresces, though less strongly than tryptophan. Its ring is reactive toward electrophiles, which allows iodination, nitration and other modifications, and in cells tyrosine is phosphorylated by tyrosine kinases and sometimes sulfated.
Role in peptides
An N-terminal tyrosine is a common feature of receptor-active peptides, including the opioid peptides and Kisspeptin-10. Tirzepatide starts with tyrosine, reflecting its GIP-derived N-terminus, whereas semaglutide starts with histidine. SS-31 uses 2',6'-dimethyltyrosine (Dmt), a modified tyrosine, in its aromatic-cationic sequence. Radioiodination of tyrosine is a long-standing way to label peptides for binding assays, and tyrosine sulfation is required for recognition in some chemokine receptor ligands. Replacing tyrosine with phenylalanine tests whether the hydroxyl group contributes to binding.
Stability and analysis
Tyrosine is moderately sensitive. Oxidative conditions and light can form dityrosine crosslinks and other oxidised products, and nitrating agents produce nitrotyrosine. During acid cleavage, the ring can be alkylated by protecting-group carbocations unless scavengers are used, and side-chain tert-butyl protection must be fully removed. Tyrosine-containing peptides should be protected from light and oxidants. Tyrosine's UV absorbance supports concentration estimates when combined with a sequence-based extinction coefficient.
In PeptideWiki compounds
Compounds whose sequence contains tyrosine, with the number of occurrences.
- IGF-1 LR3 (3)
- CJC-1295 (2)
- MOTS-c (2)
- Sermorelin (2)
- Tesamorelin (2)
- VIP (vasoactive intestinal peptide) (2)
- AOD-9604 (1)
- Afamelanotide (1)
- Calcitonin (salmon) (1)
- Gonadorelin (1)
- Kisspeptin-10 (1)
- Oxytocin (1)
- Pramlintide (1)
- Triptorelin (1)
Frequently asked questions
Why do many peptide hormones start with tyrosine?
In several receptor families, including opioid receptors, the N-terminal amine and the phenol ring of tyrosine form a key binding element together. Changing or removing this tyrosine often abolishes activity, which is why it is conserved across many natural and synthetic ligands. Modified tyrosines such as 2',6'-dimethyltyrosine are used to increase affinity or resistance to degradation while keeping this arrangement.
What is dityrosine?
Dityrosine is a crosslink formed when two tyrosine phenol rings are joined by a carbon-carbon bond after oxidation. It can link two peptide chains, creating dimers, or two positions within one chain. It is fluorescent and is used as a marker of oxidative damage in proteins. In synthetic peptides it appears as a dimer or higher-mass species and indicates exposure to oxidants or light.
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