Cagrilintide 10 mg

What is cagrilintide?

Cagrilintide is the INN of a synthetic peptide, usually spelt Cagrilintid in German. It is one of the amylin analogues: its chain of 37 amino acids follows the structure of human amylin (IAPP), but is modified at six positions and lipidated. Pharmacologically, cagrilintide is regarded as a non-selective agonist at the amylin receptors AMY1, AMY2 and AMY3 and at the calcitonin receptor (CTR). Each amylin receptor is a complex of the calcitonin receptor and one receptor activity-modifying protein (RAMP1, RAMP2 or RAMP3).

Structure and key data

Compared with human amylin, cagrilintide carries glutamic acid at position 14 and arginine at position 17, a pair designed to form a helix-stabilising salt bridge. In addition, there are prolines at positions 25, 28, 29 and 37. A fatty diacid with 20 carbon atoms is attached to the α-amino terminus of Lys1 via an L-γ-glutamyl linker; the C-terminus is amidated.

• Peptide chain (37 amino acids): KCNTATCATQ RLAEFLRHSS NNFGPILPPT NVGSNTP
• Modifications: HOOC-(CH2)18-CO-γGlu at Lys1, C-terminal prolinamide, disulfide bridge Cys2–Cys7
• Molecular formula: C194H312N54O59S2
• Molar mass: 4409.1 g/mol (without counter-ions)
• Monoisotopic mass: 4406.25 Da
• CAS number: 1415456-99-3
• PubChem CID: 171397054

Classification: cagrilintide and related peptides

Cagrilintide shares its chain length and disulfide bridge with human amylin; the natural peptide, however, ends in a tyrosinamide and is not lipidated. The analogue pramlintide already contains prolines 25, 28 and 29; cagrilintide additionally replaces asparagine 14, valine 17 and tyrosine 37. At 32 amino acids, salmon calcitonin is shorter, but it likewise ends in a prolinamide and binds to the calcitonin receptor, the common core of the amylin receptors. Cagrilintide is listed in the Incretin Analogues category, although it is not derived from an incretin: GLP-3, for example, is derived from GIP and addresses the receptors for GIP, GLP-1 and glucagon, whereas cagrilintide addresses the calcitonin receptor family. What the two have in common is the C20 fatty diacid.

Research context

Cagrilintide is studied in in-vitro and preclinical research on the amylin and calcitonin receptor system. As the same molecule addresses the calcitonin receptor alone and all three RAMP complexes, it can be used to compare how the respective RAMP subunit alters ligand recognition. This describes a subject of research, not an effect in a living organism. More on naming and structure can be found in the guide to cagrilintide.

Analytics at GPeptides

The vial contains 10 mg of lyophilised peptide with a stated purity of ≥ 98 %. Cagrilintide is regularly tested externally by HPLC and mass spectrometry; in reversed-phase HPLC, the C20 side chain prolongs retention, and the purity figure is based on the area share of the main peak. After electrospray ionisation, multiply protonated ions appear; calculated from the average mass, they lie at m/z 1470.7 (3+), 1103.3 (4+) and 882.8 (5+). At around 4.4 kDa, the monoisotopic signal reaches only about a third of the most intense isotope peak (M+2). If the fatty-acid γGlu side chain is missing, the average mass falls by around 453.6 Da; an opened disulfide bridge increases it by about 2 Da, which only high-resolution spectra detect reliably. Where a certificate of analysis (COA) is available, you will find it in the lab area; if it is missing there, the test is marked as “pending”. The basics are explained in the guide HPLC and mass spectrometry.