What is Amino acid?
Also called: Amino acid residue, AA
A molecule carrying an amine group, a carboxylic acid group and a variable side chain; peptides are chains of amino acids linked by peptide bonds.
By the APL Research Team Β· Updated
An amino acid has an amine group (βNH2) and a carboxylic acid group (βCOOH) attached to the same Ξ±-carbon, plus a side chain, the R group, that gives it its identity. Twenty amino acids are encoded by the standard genetic code; all but glycine are chiral, and proteins are built from the L forms. Once built into a chain through peptide bonds, each amino acid has lost the elements of one water molecule and is called a residue.
Free amino acid versus residue
The water lost at each bond is why residue masses, not free amino acid masses, add up to a peptide's mass:
| Amino acid | Free form (g/mol) | As a residue (g/mol) |
|---|---|---|
| Glycine (Gly, G) | 75.07 | 57.05 |
| Histidine (His, H) | 155.16 | 137.14 |
| Lysine (Lys, K) | 146.19 | 128.17 |
Building GHK, the tripeptide behind copper peptide research: the residues sum to 57.05 + 137.14 + 128.17 = 322.36, and adding one water (18.02) for the free N- and C-termini gives 340.38 g/mol, the value the peptide molecular weight calculator returns. Adding the three free amino acids instead gives 376.42, two waters too many.
Side chains decide behaviour
| Class | Members | Why it matters at the bench |
|---|---|---|
| Acidic | Asp, Glu | Negative at neutral pH; lower the isoelectric point |
| Basic | Lys, Arg, His | Positive at acidic pH; each binds a counter-ion in the dry salt |
| Hydrophobic | Leu, Ile, Val, Phe, Trp, Met | Reduce water solubility and favour aggregation |
| Oxidation-prone | Met, Cys, Trp | Sites of oxidation; Cys also forms disulfide bonds |
| Deamidation-prone | Asn, Gln | Convert to Asp and Glu over time (deamidation) |
| Structural | Pro, Gly | Pro restricts the backbone; Gly makes it more flexible |
Reading a sequence through this table predicts much of a peptide's handling: a chain heavy in Lys and Arg will dissolve readily in slightly acidic water and carry several counter-ions, while one with several Met residues will need protection from oxidation.
Beyond the standard twenty
Research peptides often contain residues the genetic code does not specify. Ipamorelin is Aib-His-D-2-Nal-D-Phe-Lys-NH2: Aib (Ξ±-aminoisobutyric acid) carries two methyl groups on its Ξ±-carbon, 2-Nal (2-naphthylalanine) is a synthetic aromatic residue, two of the five residues are D-enantiomers, and the C-terminus is an amide. Semaglutide differs from human GLP-1 by two substitutions, Aib at position 8 and Arg at position 34, and is derivatised at lysine 26; its developers aimed for full stability against metabolic degradation together with stronger albumin binding [1]. Non-standard residues like these are one of the main ways synthetic analogues are made more resistant to proteases than their natural templates.
Notation
Each amino acid has a three-letter and a one-letter code. Several one-letter codes do not match their names: F is phenylalanine, W tryptophan, Y tyrosine, Q glutamine, E glutamate, K lysine. The peptide sequence entry and the guide to reading peptide sequences cover the conventions, including modifications.
References
- 1.Lau J, Bloch P, SchΓ€ffer L, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015. PubMed 26308095