Glycine (Gly, G)
Glycine is the smallest amino acid, with a hydrogen atom as its side chain. It is the only achiral standard amino acid and gives peptide backbones exceptional flexibility.
Structure and properties
Glycine has no side chain beyond a single hydrogen, so its alpha carbon is not a stereocentre and glycine has no D or L form. The lack of a side chain lets the backbone reach conformations unavailable to other residues, including those with positive phi angles. As a result glycine is common in tight turns, loops and hinges, and generally destabilises alpha helices. It is small enough to fit where nothing else can, such as at every third position in the collagen triple helix (Gly-X-Y). Glycine has little hydrophobic or hydrophilic character of its own and influences solubility mainly through backbone exposure.
Role in peptides
Glycine provides flexibility and turn-forming ability in peptides. GHK-Cu begins with glycine, whose free amine takes part in copper coordination together with histidine. Glycine forms part of the Pro-Gly-Pro tail of Semax and Selank, and appears in BPC-157, DSIP and Kisspeptin-10. Glutathione ends in glycine. In GLP-1 analogues, glycine near the N-terminus forms part of the region recognised by the receptor. Glycine-serine repeats are widely used as flexible linkers between functional peptide or protein domains.
Stability and analysis
Glycine itself has few specific concerns. It cannot racemise and has no reactive side chain. Its main analytical relevance is as a neighbour: Asn-Gly and Asp-Gly are the fastest deamidation and isomerisation motifs because glycine leaves the backbone nitrogen unhindered. In synthesis, a glycine or proline in the first two positions from the resin can promote diketopiperazine formation and chain loss, and glycine-rich sequences may aggregate on resin.
In PeptideWiki compounds
Compounds whose sequence contains glycine, with the number of occurrences.
- IGF-1 LR3 (7)
- Exenatide (5)
- BPC-157 (3)
- Calcitonin (salmon) (3)
- DSIP (3)
- Larazotide (3)
- Tesamorelin (3)
- AOD-9604 (2)
- Gonadorelin (2)
- LL-37 (2)
- Pramlintide (2)
- Abaloparatide (1)
- Afamelanotide (1)
- Epitalon (1)
- GHK-Cu (1)
- Glutathione (1)
- Humanin (1)
- Kisspeptin-10 (1)
- MOTS-c (1)
- Oxytocin (1)
- Selank (1)
- Semax (1)
- Sermorelin (1)
- Teriparatide (1)
- Thymosin β4 (1)
- Triptorelin (1)
Frequently asked questions
Why is glycine achiral?
A chiral carbon needs four different substituents. Glycine's alpha carbon carries an amine, a carboxyl and two hydrogens, so two substituents are identical and no mirror-image form exists. This is why glycine is the only standard amino acid without D and L forms. Practically, it means glycine cannot racemise during peptide synthesis, removing one source of impurity that affects other residues.
Why does glycine break helices?
Helix formation requires the backbone to adopt a fixed set of angles. Glycine's lack of a side chain gives it so much conformational freedom that holding it in a helix costs more entropy than for other residues. It also lacks side-chain interactions that help stabilise helices. Glycine is therefore enriched in loops, turns and helix termini, and is often used where a flexible hinge is wanted.
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