Asparagine (Asn, N)
Asparagine is a polar, uncharged amino acid with a side-chain amide. It is common in turns and glycosylation sites and is the residue most prone to deamidation in peptides.
Structure and properties
Asparagine carries a short side chain ending in a carboxamide group. The amide is polar and uncharged, acting as both hydrogen-bond donor and acceptor, so asparagine is hydrophilic and usually found on protein surfaces. Because the side chain is short, its amide can hydrogen bond to the peptide backbone, which helps asparagine cap helices and stabilise tight turns. In proteins, asparagine within the sequon Asn-X-Ser/Thr (where X is not proline) is the attachment site for N-linked glycans. Asparagine is the amide counterpart of aspartic acid, and conversion between the two by deamidation is one of the most important degradation routes in peptide chemistry.
Role in peptides
Asparagine is frequently found at turn positions and at the N-terminal caps of helices, where its side chain satisfies backbone hydrogen bonds. In short bioactive peptides it often supports receptor recognition through hydrogen bonding rather than hydrophobic contact. Kisspeptin-10 contains two asparagines in its sequence Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, and asparagine appears in many larger hormone and antimicrobial sequences. Designers sometimes replace asparagine with glutamine or another residue to reduce deamidation risk, although this can change activity when the amide side chain contributes directly to binding.
Stability and analysis
Deamidation is the main concern. The backbone nitrogen of the following residue attacks the side-chain amide to form a succinimide, which hydrolyses to a mixture of aspartate and isoaspartate. The reaction is fastest when asparagine is followed by glycine or serine, and accelerates at neutral-to-basic pH and higher temperature. Products differ in mass by about one dalton and often elute close to the parent on HPLC. In synthesis, unprotected asparagine can dehydrate to a nitrile, so trityl side-chain protection is standard.
In PeptideWiki compounds
Compounds whose sequence contains asparagine, with the number of occurrences.
- Pramlintide (6)
- Teriparatide (3)
- VIP (vasoactive intestinal peptide) (3)
- Calcitonin (salmon) (2)
- IGF-1 LR3 (2)
- Kisspeptin-10 (2)
- Tesamorelin (2)
- ARA-290 (cibinetide) (1)
- Exenatide (1)
- LL-37 (1)
- Oxytocin (1)
- Sermorelin (1)
- Thymosin α1 (1)
- Thymosin β4 (1)
Frequently asked questions
What is asparagine deamidation?
Deamidation is the non-enzymatic loss of the side-chain amide nitrogen, converting asparagine into aspartate or isoaspartate through a cyclic succinimide intermediate. It adds a negative charge and, for isoaspartate, inserts an extra carbon into the backbone. It is a leading cause of chemical instability in peptide and protein products, especially in solution at neutral or basic pH, and is monitored by HPLC and high-resolution mass spectrometry.
Which sequences deamidate fastest?
Asn-Gly is the most labile motif, because glycine's lack of a side chain lets the backbone nitrogen reach the asparagine amide easily. Asn-Ser, Asn-Ala and Asn-His also deamidate relatively quickly. Local structure matters: asparagines held in rigid helices or buried in folded regions react more slowly than those in flexible, exposed segments. Storing peptides lyophilized and cold, and avoiding prolonged time in neutral or basic buffers, limits the reaction.
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