Aspartic acid (Asp, D)
Aspartic acid (aspartate) is an acidic amino acid with a short carboxylate side chain. It provides negative charge in recognition motifs such as RGD and is prone to isomerisation and aspartimide formation.
Structure and properties
Aspartic acid has a short side chain ending in a carboxylic acid that is deprotonated, and so negatively charged, at physiological pH. The short chain places the carboxylate close to the backbone, letting it cap helices and form hydrogen bonds or salt bridges with nearby basic residues. Aspartate is strongly hydrophilic and nearly always solvent-exposed. It also binds metal ions such as calcium, often in cooperation with neighbouring acidic residues. Its amide form is asparagine. The proximity of the side-chain carboxyl to the backbone, which makes aspartate useful structurally, is also the origin of its characteristic cyclisation chemistry.
Role in peptides
Aspartate supplies negative charge in many recognition motifs, most famously Arg-Gly-Asp (RGD) for integrin binding. In cyclic melanocortin analogues such as PT-141 and Melanotan II, an aspartate side chain forms a lactam bridge with lysine to close the ring. Short regulatory peptides including epitalon (Ala-Glu-Asp-Gly) and pinealon (Glu-Asp-Arg) are acidic largely because of aspartate. BPC-157 contains two adjacent aspartates, and DSIP contains aspartate in an Asp-Ala-Ser stretch. Replacing aspartate with asparagine or glutamate is a common structure-activity test of whether charge or side-chain length matters.
Stability and analysis
Aspartate can cyclise through its backbone to a succinimide, which reopens to isoaspartate; Asp-Gly is the most susceptible motif. Asp-Pro bonds are unusually acid-labile and can cleave under strong acid. During Fmoc synthesis, repeated base treatment can drive aspartimide formation, producing isoaspartate and piperidide by-products that are hard to separate. Isoaspartate has the same mass as aspartate, so detection relies on HPLC retention shifts or specialised fragmentation methods rather than intact mass alone.
In PeptideWiki compounds
Compounds whose sequence contains aspartic acid, with the number of occurrences.
- IGF-1 LR3 (4)
- Thymosin α1 (3)
- Thymosin β4 (3)
- Abaloparatide (2)
- BPC-157 (2)
- CJC-1295 (2)
- LL-37 (2)
- Sermorelin (2)
- Tesamorelin (2)
- VIP (vasoactive intestinal peptide) (2)
- DSIP (1)
- Epitalon (1)
- Exenatide (1)
- Humanin (1)
- Melanotan II (1)
- PT-141 (bremelanotide) (1)
- Pinealon (1)
- Snap-8 (1)
- Teriparatide (1)
Frequently asked questions
What is aspartimide formation?
Aspartimide formation is a side reaction in which the backbone nitrogen after an aspartate attacks the side-chain ester or acid, forming a five-membered ring. In Fmoc solid-phase synthesis it is promoted by the piperidine used for deprotection, especially at Asp-Gly, Asp-Asn and Asp-Ser. The ring then opens to give alpha- and beta-linked products and, often, racemised material. Bulky side-chain protecting groups and modified deprotection conditions reduce it.
Can mass spectrometry detect isoaspartate?
Not from intact mass, because aspartate and isoaspartate are isomers with identical mass. Isoaspartate usually changes HPLC retention slightly, and certain fragmentation techniques, such as electron-transfer or electron-capture dissociation, produce diagnostic fragments. Enzymatic assays using protein isoaspartyl methyltransferase are also used. A standard certificate of analysis based on intact mass and a single HPLC trace may not reveal low levels of isoaspartate.
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