Amino acid sequence

An amino acid sequence is the order in which amino acids are linked by peptide bonds, written from the N-terminus to the C-terminus. Each of the 20 standard amino acids has a one-letter code: H for histidine, A for alanine, E for glutamic acid, G for glycine, K for lysine, R for arginine, and so on. A sequence is a string of those letters.

An example: GLP-1 and its drugs

Human GLP-1(7-37), the active form of the gut peptide, is 31 amino acids long:

HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG

The drugs are variations on that string. Each label states how close it is:

Positions in GLP-1 drugs are numbered from 7, because GLP-1 is cut from a longer precursor and the active peptide starts at its seventh residue. That is why the first alanine of the string above is "position 8".

Letters that are not on the list

Aib, the aminoisobutyric acid in semaglutide and tirzepatide, is not one of the 20 standard amino acids, so it has no standard one-letter code. Sequences write it as Aib or as X with a footnote. Fatty acid side chains, C-terminal amides and other modifications are shown in brackets or notes. A plain string of the 20 letters can therefore leave out exactly the changes that turn a gut peptide into a weekly drug.

Homology is not equivalence

Ninety-four percent homology means most positions match. It does not mean the molecule behaves 94 percent like the original. A single change at position 8 is the difference between a two-minute and a week-long half-life. Small sequence changes can also alter which receptors a peptide binds, how it folds, how it aggregates in solution and whether the immune system notices it.

The same logic cuts the other way for research peptides. A product sold under a familiar name is only that compound if the sequence matches. A vial with one amino acid missing, or one swapped, can look identical and carry the same label.

How a sequence is checked

Mass spectrometry measures the molecular weight, which confirms the sequence adds up to the right mass. It cannot always tell the order of the letters on its own, and it cannot separate leucine from isoleucine by mass, because the two weigh the same. Fragmentation methods (tandem mass spectrometry) break the chain and read the pieces, which confirms order. HPLC shows how much of the sample is the main compound. A certificate of analysis should say which of these tests were run, and on which batch.

The compound library in the app lists what each compound is and how much research exists on it. When you log a vial in the vial tracker, the batch and source sit beside every dose taken from it.

Related terms: peptide bond, mass spectrometry, certificate of analysis, receptor agonist. Back to the glossary.