Tryptophan (Trp, W)
Tryptophan is the largest standard amino acid, with an indole side chain. It is strongly UV-absorbing and fluorescent, anchors peptides at membranes and is highly sensitive to oxidation and light.
Structure and properties
Tryptophan carries an indole group, a fused benzene and pyrrole ring system. It is the bulkiest standard side chain and is largely hydrophobic, though the indole nitrogen can donate a hydrogen bond. Tryptophan prefers the interfacial region of lipid membranes, where it anchors peptides and proteins. Its indole dominates the ultraviolet absorbance of proteins and is intrinsically fluorescent, with emission that shifts according to the polarity of its surroundings, a widely used probe of folding and binding. Tryptophan is the least abundant amino acid in most proteins and is often found at functionally important sites.
Role in peptides
Tryptophan is a frequent receptor-contact residue. It completes the His-Phe-Arg-Trp melanocortin core in Melanotan II and PT-141. GHRP-6 contains both D-tryptophan and L-tryptophan, and Kisspeptin-10 has tryptophan at position three. DSIP begins with tryptophan, and GLP-1 analogues including semaglutide retain a tryptophan in their C-terminal helix. Tryptophan-rich antimicrobial peptides use the indole to embed at membrane interfaces. Because tryptophan is rare and bulky, it is often critical to activity, and substitutions with other aromatic residues are a standard structure-activity probe. Its fluorescence is also used to monitor binding of tryptophan-containing peptides in vitro.
Stability and analysis
Tryptophan is easily oxidised by light, oxygen, peroxides and metal-catalysed reactions, forming products such as N-formylkynurenine, kynurenine and oxindolylalanine that show as added-oxygen species by mass spectrometry. During acid cleavage, carbocations from protecting groups can alkylate the indole unless scavengers and Boc indole protection are used. Store tryptophan-containing peptides protected from light, cold and dry. Its strong UV absorbance makes it useful for quantitation when the extinction coefficient is known.
In PeptideWiki compounds
Compounds whose sequence contains tryptophan, with the number of occurrences.
- GHRP-6 (2)
- Triptorelin (2)
- Afamelanotide (1)
- DSIP (1)
- Exenatide (1)
- GHRP-2 (1)
- Gonadorelin (1)
- Kisspeptin-10 (1)
- MOTS-c (1)
- Melanotan II (1)
- PT-141 (bremelanotide) (1)
- Setmelanotide (1)
- Teriparatide (1)
Frequently asked questions
Why is tryptophan used to quantify peptides?
The indole ring absorbs ultraviolet light strongly, more than any other standard side chain. Together with tyrosine and cystine, it lets the concentration of a peptide solution be estimated from absorbance using an extinction coefficient calculated from the sequence. For peptides without tryptophan or tyrosine, other methods such as amino acid analysis are needed.
What does tryptophan oxidation produce?
Oxidation can open or modify the indole ring. Common products include oxindolylalanine and hydroxytryptophan, which add one oxygen, N-formylkynurenine, which adds two, and kynurenine, formed after loss of formate. These species usually appear as earlier-eluting HPLC peaks and as characteristic mass shifts. Light exposure, peroxide contaminants and trace metals all accelerate the process, so storage away from light is important.
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