GLP-3

GLP-3, developed under the code LY3437943, is a synthetic 39-residue lipidated peptide. Structurally it is one of the more elaborate molecules in this library: a peptide backbone carrying three separate non-natural residues, a C-terminal amide, and a long fatty-diacid chain attached through a two-part linker. Each of those features is a deliberate synthetic choice, and together they are what distinguish it from the shorter, unmodified peptides elsewhere in the catalogue.

Identity and classification

GLP-3 is catalogued pharmacologically as a triple agonist at three related class B G-protein-coupled receptors: the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. That classification describes which receptors the molecule was designed to engage. It is a statement about molecular pharmacology, not about any outcome, and nothing further should be read into it.

The peptide sits in the incretin-analogue structural family, which is a design lineage rather than a formal chemical class — a group of synthetic peptides sharing a common architecture of a GLP-1-like backbone, non-natural residues at protease-labile positions, and a lipid chain for albumin binding.

Structure

The 39-residue sequence carries three modifications that are not available from the standard amino acid set:

• α-Aminoisobutyric acid (Aib) at positions 2 and 20. Aib is a doubly methylated alanine with no chiral centre. At position 2 it occupies the site that would otherwise be the primary target of dipeptidyl peptidase-4 cleavage; substituting a non-natural residue there is the standard synthetic route to a protease-resistant incretin backbone.
• α-Methyl-leucine at position 13. A further backbone methylation, again at a position where conformational restriction is wanted.
• C-terminal serinamide. The chain terminates in an amide rather than a free acid, removing the terminal negative charge.
• Lysine-17 side-chain acylation. The ε-amino group of Lys17 carries an AEEA–AEEA–γGlu spacer terminating in a C20 fatty diacid. The two AEEA units are short polyethylene-glycol-like spacers; the γ-glutamate is a charged linker; the C20 diacid is the albumin-binding element. This whole assembly accounts for a substantial fraction of the molecular formula.

The result is a molecule with three distinct chemical regions — peptide backbone, hydrophilic linker, lipid tail — and that heterogeneity is exactly what makes it analytically demanding.

Specification and characterisation

• RP-HPLC purity. The C20 diacid makes this peptide considerably more hydrophobic than an unmodified 39-mer, and it retains strongly on C18. Elevated column temperature and a shallow acetonitrile gradient are usually required to produce a symmetrical peak; a broad or tailing peak is frequently a chromatography artefact rather than a purity problem.
• Mass confirmation. Against an average mass of 4731.4 and a monoisotopic mass of 4728.47. At this size high-resolution ESI-MS resolves the isotope envelope; lower-resolution instruments report the average.
• Acylation-related impurities. The characteristic synthesis-related impurities are the des-acyl peptide, where side-chain acylation failed, and the bis-acylated species, where a second lysine or the N-terminus was acylated. Both are mass-resolvable and both are the impurities worth asking a certificate about.
• Deletion sequences. A 39-residue synthesis accumulates single-residue deletions; these appear as masses one residue below the target and are the reason a purity figure for a long peptide means less than the same figure for a tetrapeptide.
• Net peptide content and counter-ion. Amino acid analysis and ion chromatography, as for any salt-form peptide.

Handling and stability

Store sealed at 2–8 °C, dry, protected from light. Equilibrate in a desiccator before opening. There is no cysteine and no methionine in the sequence, so neither disulfide scrambling nor sulfoxide formation is a concern — unusual among the longer peptides here, and it makes glp-3 comparatively robust as a dry solid.

The lipid chain does affect solution behaviour: like other acylated peptides, glp-3 has a pronounced tendency to self-associate and to adsorb to surfaces, particularly at low concentration and near neutral pH. Adsorptive loss to labware is a real and frequently unrecognised source of error with molecules of this type.

Salt form

GLP-3 is commonly supplied as the acetate salt. Where that is the case, the peptide content of the vial is below 100% by the mass of the counter-ion, and the registry number quoted above refers to the free peptide. Read the certificate for the form actually supplied.

Related compounds in this library

Tesamorelin is the closest analogue in design intent — also a long synthetic peptide analogue of a native hormone, also modified at the N-terminal region to resist dipeptidyl peptidase-4, though tesamorelin achieves it by N-terminal acylation rather than by an Aib substitution.

References

Chemical, specification and analytical sources. This list is deliberately limited to chemistry and analytical references.

• Selleck Chemicals, glp-3 product record — formula, molecular weight, sequence
• MedKoo Biosciences record 63214 — formula, average and exact mass
• BOC Sciences, CAS 2381089-83-2 — registry and formula confirmation
• Bachem, Handling and Storage Guidelines for Peptides — lyophilised solid handling, adsorption and solubility behaviour

Cosmic Aminos supplies this material as a laboratory reagent for in-vitro research use only. It is not a drug, food, cosmetic or dietary supplement, is not approved by the Food and Drug Administration for any use, and is not for human or veterinary consumption. No dosing, administration or preparation guidance is provided.