Peptide Bonds and Sequence Notation

A peptide is a chain of amino acids. Each amino acid has an amine group, a carboxylic acid group and a side chain that gives it its identity. When the carboxyl group of one amino acid reacts with the amine group of the next, a molecule of water is lost and an amide linkage forms between them: the peptide bond. Repeating this reaction produces a chain with a free amine at one end, the N-terminus, and a free carboxylic acid at the other, the C-terminus. Sequences are always written from N-terminus to C-terminus.

The twenty standard amino acids each have a three-letter and a one-letter code. Glycine is Gly or G, histidine His or H, lysine Lys or K. GHK-Cu is therefore the tripeptide glycyl-histidyl-lysine. BPC-157 written out is Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, or GEPPPGKPADDAGLV in one-letter form. Three-letter codes are used when a sequence contains unusual residues that have no single-letter code.

The boundaries are conventional rather than chemical. Chains of up to roughly fifty residues are called peptides; longer chains are polypeptides; a polypeptide folded into a stable functional structure is a protein. Di-, tri-, tetra- and pentapeptides name chains of two to five residues; a pentadecapeptide such as BPC-157 has fifteen. Tirzepatide and retatrutide at thirty-nine residues and tesamorelin at forty-four sit near the top of the peptide range.

Research peptide names often include modifications. An 'Ac-' prefix means the N-terminus is acetylated, which removes its positive charge and protects it from aminopeptidases; TB-500 is Ac-LKKTETQ. A '-NH2' suffix means the C-terminus is an amide rather than a free acid, which likewise improves stability; ipamorelin and SS-31 are C-terminal amides. A 'D-' before a residue indicates the D-enantiomer rather than the natural L-form, used to resist enzymatic cleavage, as in the D-Arg of SS-31 and the D-Phe of ipamorelin.

Non-standard residues appear with their own abbreviations: Aib is 2-aminoisobutyric acid, used in semaglutide, tirzepatide and ipamorelin; Dmt is 2′,6′-dimethyltyrosine in SS-31; Nle is norleucine in PT-141; 2-Nal is 2-naphthylalanine in ipamorelin. Lipidated peptides such as semaglutide and tirzepatide carry a fatty-diacid chain attached to a lysine side chain through a linker, which is described in the name of the full chemical entity rather than in the one-letter sequence.

Some peptides are closed into a ring by a bond between two side chains or between the termini. PT-141 is cyclised through a lactam bridge between an aspartate and a lysine side chain, written as cyclo[Asp-His-D-Phe-Arg-Trp-Lys]. Cyclisation restricts the shape the peptide can adopt and usually increases its stability and receptor selectivity.

Mass spectrometry confirms identity by matching the observed molecular weight to the theoretical value calculated from the exact sequence including every modification. A missing acetyl group, a free acid instead of an amide, or an L-residue where a D-residue was specified changes the expected mass or the chromatographic behaviour. Knowing how to read the sequence is what lets you check that the certificate describes the molecule you intended to buy.