Semaglutide
NN9535
Semaglutide is a 31-residue GLP-1 receptor agonist analogue with an Aib substitution at position 8 and a C18 diacid side chain, widely used as a reference standard in incretin-receptor research.
Analytical specification
| CAS number | 910463-68-2 |
|---|---|
| Molecular formula | C187H291N45O59 |
| Average molecular weight | 4,113.58 g/mol |
| Amino-acid count | 31 |
| Peptide class | acylated GLP-1 analogue |
| Physical form | Lyophilized powder |
| Research area | Metabolic research |
| Solubility | Soluble in sterile or bacteriostatic water; consult the lot COA for solvent guidance |
Reference values from public analytical chemistry. Confirm against the lot Certificate of Analysis before use in an assay.
Two problems, two modifications
Native GLP-1 fails on two independent counts, and semaglutide addresses each separately.
Dipeptidyl peptidase-4 inactivates native GLP-1 within minutes by cleaving after alanine 8. Semaglutide substitutes Aib — 2-aminoisobutyric acid — at that position. Its two alpha-carbon methyls make it achiral and sterically hindered, and DPP-4 cannot process it.
Renal filtration clears a 4,000-dalton peptide within hours even when protected from enzymes. Semaglutide attaches a C18 fatty diacid to lysine 26 through a linker built from gamma-glutamate and two short ethylene glycol spacers. The fatty acid binds reversibly to serum albumin; the complex is far too large to be filtered, and only the small free fraction is available for clearance or for receptor engagement.
Either modification alone would be insufficient — the two address different mechanisms and their effect is multiplicative.
Handling
The C18 diacid makes this molecule considerably more hydrophobic than an unmodified 31-mer: late reversed-phase retention, meaningful adsorption to labware, and — unusually — greater aggregation risk in concentrated solution than dilute, since the exposed lipid seeks a hydrophobic environment and often finds another semaglutide molecule.
Available as
Documentation
Certificates of Analysis are published per lot on release. Look up a lot number to retrieve its certificate.