What Is GLP-3? Structure and Chemistry

GLP-3 is retatrutide, a synthetic lipidated peptide and, by receptor class, a GIP, GLP-1 and glucagon receptor agonist peptide. It is catalogued under CAS 2381089-83-2, with the molecular formula C221H342N46O68 and an average molecular weight of 4731.4 g/mol. Its 39-residue chain carries three non-coded amino acids and ends in a C-terminal amide, and the side chain of lysine 17 carries a C20 fatty diacid attached through a short hydrophilic linker.

The 39-residue sequence

GLP-3 is a linear chain with a free N-terminal amine on Tyr1 and an amidated C-terminal serine. The table sets the sequence out in blocks of ten in three-letter code, with the modified positions marked.

In one-letter code, with the non-coded residues written out, the chain reads Y-Aib-QGTFTSDYSI-αMeL-LDKKAQ-Aib-AFIEYLLEGGPSSGAPPPS-NH2. It has two adjacent lysines: Lys16 is unmodified and Lys17 carries the lipidated side chain. The last nine residues, Pro31 to the C-terminal serine amide, form a proline-rich tail with three consecutive prolines at positions 36–38.

If you are new to these conventions, peptide sequence notation covers three-letter and one-letter codes and how terminal groups are written.

Three non-coded residues

Three positions in the chain are amino acids that the genetic code does not encode. All three carry a methyl group on the α-carbon in place of the α-hydrogen.

An α,α-disubstituted residue has no α-hydrogen and a narrower range of backbone torsion angles than its parent amino acid. Aib in particular is a strongly helix-favouring residue in peptide chemistry, and the extra methyl groups crowd the neighbouring peptide bonds sterically. In GLP-3, Aib2 sits directly after the N-terminal tyrosine, while αMeLeu13 and Aib20 sit in the middle of the chain on either side of the lipidated lysine.

The lipidated side chain on lysine 17

The ε-amino group of Lys17 is acylated by a linker of two units, and the linker ends in a long-chain fatty diacid. The full IUPAC name in PubChem confirms each unit and its order.

Each junction is an amide bond. The single OEG spacer gives a shorter linker than the two-spacer linker on tirzepatide, and the formula reflects it. Together, the spacer, the γGlu unit and the diacid make GLP-3 an amphiphilic molecule: a peptide chain carrying a long hydrocarbon tail that ends in a carboxylic acid.

With two neighbouring lysines, putting the side chain on Lys17 and not on Lys16 is a regioselectivity problem. In solid-phase synthesis it is normally solved by giving the lysine to be modified an orthogonal side-chain protecting group, removed on the resin before the linker units are coupled. Solid-phase peptide synthesis explains the approach.

Formula, mass and expected ions

The formula C221H342N46O68 describes the complete neutral molecule: peptide chain, linker and diacid together. Building it up from the 39 residues, the OEG spacer, the γGlu unit, the diacid and the C-terminal amide reproduces the formula PubChem lists, and the calculated monoisotopic mass, 4728.47 Da, matches PubChem's value.

Calculated average masses differ in the second decimal place with the atomic-weight table used: 4731.35 g/mol with the older standard atomic weights and 4731.42 g/mol with the current IUPAC abridged values. Both round to the catalogue's 4731.4 g/mol; the difference reflects the reference table, not the molecule.

At about 4.7 kDa, GLP-3 appears in electrospray ionisation mass spectrometry as a series of multiply protonated ions rather than one singly charged ion. Calculated from the average mass, the main charge states fall at:

For a molecule this size the isotope envelope is broad and the monoisotopic peak is not the most abundant one, so deconvoluted spectra are usually compared with the average mass. Mass spectrometry for peptide identity explains charge states and deconvolution in more detail.

Receptor binding at the molecular level

By receptor class, GLP-3 is a GIP, GLP-1 and glucagon receptor agonist peptide: one chain that binds and activates three different receptors. All three belong to class B1 of the G protein-coupled receptors (GPCRs), the secretin-like family. Its members combine a large N-terminal extracellular domain with the seven-helix transmembrane domain common to all GPCRs, and they bind peptide ligands through both domains.

Peptide ligands of this family share a common binding mode: the C-terminal part of the helix is held by the extracellular domain, while the N-terminal residues reach into the transmembrane core. In GLP-3, that N-terminal segment begins Tyr1–Aib2–Gln3, and the three α-methylated residues sit along the helical stretch of the chain.

How GLP-3 is characterised analytically

Two complementary methods establish the identity and purity of a lipidated peptide like GLP-3.

• Reversed-phase HPLC separates the main peptide from related substances and reports purity as the main peak's share of total peak area, with UV or photodiode-array (PDA) detection. The C20 diacid adds a long hydrocarbon chain, so a lipidated peptide is retained more strongly on C8 or C18 columns than a non-lipidated chain of similar length. HPLC and peptide purity covers the method.
• LC-MS confirms identity by matching the observed mass, deconvoluted from the charge states above, to the expected mass.

The impurities these methods look for are those typical of solid-phase synthesis: deletion sequences missing a residue, truncated chains, incompletely deprotected species and, for a lipidated peptide, chains carrying an incomplete linker or the side chain on the wrong lysine.

Our GLP-3 is supplied at ≥99% purity (HPLC) and is independently tested by PeptideVerify. Report PV-82D8C6-XTFK, prepared for British Peptide Labs and issued on 6 August 2026 (HPLC-PDA and LC-MS), is published in the COA Library. How to read a peptide certificate of analysis walks through each line of a report like it.

Form and storage of the sealed vial

GLP-3 is supplied as a white to off-white lyophilised powder in a sealed vial, in 10 mg, 20 mg, 30 mg and 40 mg presentations. Identifiers, prices and availability are listed on the GLP-3 product page.

Store the sealed vial at 2–8 °C for short-term storage, or at −20 °C and below for long term. Protect it from light and avoid repeated freeze-thaw cycles. Handle the material as a laboratory chemical, following your institution's chemical-safety procedures. Storing lyophilised peptides explains why cold, dark and dry storage matters for a freeze-dried solid.

In our catalogue, GLP-3 sits in the Incretin & Amylin Analogues research area, alongside tirzepatide, semaglutide and cagrilintide. Terms used here, such as lipidation, counter-ion and monoisotopic mass, are defined in the glossary.