What Is Cagrilintide? Structure and Chemistry

Cagrilintide is a synthetic lipidated peptide of 37 amino acid residues, built as an analogue of the peptide amylin. A disulphide bridge between Cys2 and Cys7 closes a small ring at the N-terminal end, and the chain ends in a C-terminal prolinamide. The N-terminal amine carries a C20 fatty diacid attached through a γ-glutamic acid linker. PubChem lists its molecular formula as C194H312N54O59S2, with a molecular weight of about 4409 g/mol. At the molecular level it is an agonist peptide at the amylin and calcitonin receptors.

The 37-residue sequence

Cagrilintide's chain runs from lysine at position 1 to an amidated proline at position 37. The table sets it out in blocks of ten in three-letter code, with the structural features marked.

In one-letter code the chain reads KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH2. The disulphide bond joins the side chains of Cys2 and Cys7 and encloses a six-residue ring: Cys-Asn-Thr-Ala-Thr-Cys. Lys1 is modified at its α-amine, not its side chain, so the ε-amine of Lys1 stays free.

PubChem's systematic synonym numbers the same molecule differently. It lists the γ-glutamyl unit as the first residue, so the disulphide appears as "cyclic (3→8)". Counted along the peptide chain alone, that is Cys2–Cys7. Peptide sequence notation covers how residues, bridges and terminal groups are written.

Six substitutions relative to the native sequence

Human amylin is also a 37-residue peptide with a Cys2–Cys7 disulphide and an amidated C-terminus. Cagrilintide keeps that framework and changes six positions.

Two chemical themes run through these changes.

The Glu14–Arg17 pair. Human amylin is known for its strong tendency to form amyloid fibrils. Glu14 and Arg17 sit three residues apart, about one turn of an α-helix, where their opposite charges can form an intramolecular salt bridge. Cao et al. (2025) describe the pair as helix-stabilising substitutions introduced to counteract fibril formation, and note that the salt bridge is visible in the crystal structure of the non-lipidated cagrilintide backbone fused to maltose-binding protein (PDB 7BG0), across an N-terminal helix spanning residues 5–18.

The prolines. Proline's side chain loops back onto its own backbone nitrogen. That locks one backbone torsion angle and removes the amide N–H that β-sheets use for hydrogen bonding. Proline is therefore a well-established disruptor of the extended β-strands that assemble into amyloid fibrils. Human amylin contains no proline at all; cagrilintide carries four, at positions 25, 28, 29 and 37, with 28 and 29 forming a Pro-Pro pair.

The N-terminal lipidation

Cagrilintide's lipid is attached at the start of the chain rather than on a lysine side chain.

PubChem names the lipid group "19-carboxy-1-oxononadecyl": a twenty-carbon diacid attached through one end. There is no ethylene-glycol spacer between the lipid and the peptide.

Building the formula up confirms this arrangement. The 37 residues, plus the γGlu unit and the C20 diacid, minus two hydrogens for the disulphide and with the C-terminal amide, give C194H312N54O59S2, exactly the formula PubChem lists.

In the 2025 cryo-EM structures, the lipid is poorly resolved. Limited density is visible only for the γGlu linker and a short segment of the acyl chain, and only in high-resolution maps focused on the receptor. The authors also determined structures with a cagrilintide analogue lacking the lipid. With the peptide stably bound, lipidation changed neither its conformation nor the receptor's, apart from the orientation of Lys1, the attachment site.

Formula, mass and expected ions

PubChem lists the formula C194H312N54O59S2, rounds the molecular weight to 4409 g/mol and gives the monoisotopic mass as 4406.2515 Da. Calculated from the formula, the average mass is 4409.01 g/mol with the older standard atomic weights (C 12.0107, H 1.00794, N 14.0067, O 15.9994, S 32.065) and 4409.07 g/mol with the current IUPAC abridged values. The difference is under 0.01% and reflects the reference table, not the molecule.

In electrospray ionisation mass spectrometry, cagrilintide appears as a series of multiply protonated ions. Calculated from the average mass, the main charge states fall at:

The disulphide gives mass spectrometry a useful check. Reduction of the Cys2–Cys7 bond adds two hydrogen atoms, so the reduced chain is 2.02 Da heavier than the intact molecule. Comparing the spectrum of the intact peptide with that of a reduced sample confirms that the bridge is present. Mass spectrometry for peptide identity explains charge states and deconvolution.

Receptor binding at the molecular level

Cagrilintide is an agonist peptide at the amylin receptors and at the calcitonin receptor. The receptor system is modular. The calcitonin receptor is a class B1 G protein-coupled receptor. When it pairs with one of three receptor activity-modifying proteins (RAMP1, RAMP2 or RAMP3), it forms the three amylin receptors, AMY1, AMY2 and AMY3.

Cao et al. (2025) determined cryo-EM structures of cagrilintide bound to all three amylin receptors and to the calcitonin receptor alone, each in the active state and coupled to the heterotrimeric Gs protein. The AMY2 complex is PDB 9BQ3, at 2.8 Å. The structures show:

• an amylin-like binding mode, including a "bypass" motif formed by residues Ser19 to Pro25
• the Glu14–Arg17 salt bridge present in the receptor-bound peptide
• the small side chain of the C-terminal Pro37 buried among hydrophobic residues of the calcitonin receptor's extracellular domain

How cagrilintide is characterised analytically

Two complementary methods establish identity and purity:

• 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 detection at 214–220 nm. HPLC and peptide purity explains the method.
• Mass spectrometry confirms identity against the expected mass, and the reduction check above confirms the disulphide.

Typical related substances from solid-phase synthesis are deletion and truncated sequences and incompletely deprotected chains. A disulphide-bridged peptide adds two more: chains left in the reduced form and disulphide-linked dimers. A lipidated peptide can also carry an incomplete lipid group.

For our cagrilintide, purity is specified as ≥99% (HPLC, supplier specification). Certificate status is shown on every product page, and a batch certificate is available on request.

Form and storage of the sealed vial

Cagrilintide is supplied as a white to off-white lyophilised powder in a sealed vial, in a 10 mg presentation. Details are on the cagrilintide 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 a freeze-dried solid is kept cold, dark and dry.

In our catalogue, cagrilintide sits in the Incretin & Amylin Analogues research area, which groups lipidated peptide analogues by molecular class. Terms such as disulphide bridge, lyophilisation and monoisotopic mass are defined in the glossary.