Threonine (Thr, T)
Threonine is a polar, beta-branched amino acid with a hydroxyl side chain and two stereocentres. It is a phosphorylation and O-glycosylation site and favours beta-strand structure.
Structure and properties
Threonine has a side chain carrying both a hydroxyl and a methyl group on the beta carbon. This beta branching gives it a second stereocentre and restricts its conformation, favouring extended beta-strand structure. The hydroxyl makes threonine polar and able to hydrogen bond, while the methyl adds some hydrophobic character, so threonine is found both on surfaces and at interfaces. Natural L-threonine has a defined configuration at both stereocentres; inverting the beta carbon gives allo-threonine. In cells, threonine is phosphorylated by serine/threonine kinases and is a common site for O-linked glycosylation.
Role in peptides
Threonine begins Selank, whose N-terminal Thr-Lys-Pro-Arg is the tuftsin sequence. GLP-1 contains threonine near its N-terminus, retained in semaglutide and similar analogues. Threonine-rich regions often form beta strands or carry dense O-glycosylation, as in mucins. Its beta branching makes it a useful probe in structure-activity studies, and threonine in the sequon Asn-X-Thr directs N-glycosylation. Synthetic threonine-containing peptides are widely used as kinase substrates. Replacing threonine with serine or valine separates the contribution of its hydroxyl from that of its methyl group.
Stability and analysis
Threonine is generally stable. Like serine, it can undergo an acid-catalysed N-to-O acyl shift and base-induced beta-elimination, particularly when phosphorylated. Beta branching slows couplings and can contribute to on-resin aggregation. Epimerisation at the alpha carbon during synthesis gives D-allo-threonine, a diastereomer that may appear as a closely eluting HPLC peak. Side-chain tert-butyl protection is standard and must be removed fully during cleavage.
In PeptideWiki compounds
Compounds whose sequence contains threonine, with the number of occurrences.
- Calcitonin (salmon) (5)
- Pramlintide (5)
- IGF-1 LR3 (3)
- Thymosin α1 (3)
- Thymosin β4 (3)
- Exenatide (2)
- Matrixyl (palmitoyl pentapeptide-4) (2)
- TB-500 (2)
- VIP (vasoactive intestinal peptide) (2)
- Abaloparatide (1)
- CJC-1295 (1)
- Humanin (1)
- LL-37 (1)
- Selank (1)
- Sermorelin (1)
- Tesamorelin (1)
Frequently asked questions
How does threonine differ from serine?
Both carry a side-chain hydroxyl, but threonine adds a methyl group on the beta carbon. That makes threonine beta-branched, more hydrophobic and more restricted in conformation, with a preference for beta strands. It also gives threonine a second stereocentre, which serine lacks. Both are phosphorylated and glycosylated, though their kinase specificities and roles in protein structure differ.
What is tuftsin?
Tuftsin is the tetrapeptide Thr-Lys-Pro-Arg, a fragment of an immunoglobulin heavy chain that has been studied for effects on phagocytic cells in vitro and in animal models. Selank was designed by extending tuftsin with a Pro-Gly-Pro sequence intended to slow enzymatic degradation. The threonine at the N-terminus is retained in Selank, so the two share their first four residues.
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