Semaglutide¶
Semaglutide (CAS 910463-68-2) is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist with a molecular weight of 4,113.6 Da. Engineered with a C18 fatty diacid side chain and Aib substitution at position 8, it achieves albumin binding and resistance to DPP-4 degradation, yielding a prolonged half-life suitable for once-weekly research protocols. As a GLP-1 receptor agonist, it activates cAMP/PKA signaling to enhance glucose-dependent insulin secretion and suppress glucagon.
Technical Specifications¶
| Property | Value |
|---|---|
| CAS Number | 910463-68-2 |
| Molecular Formula | C₁₈₇H₂₉₁N₄₅O₅₉ |
| Molecular Weight | 4,113.6 Da |
| Purity | ≥99% (HPLC-verified) |
| Appearance | Lyophilized white powder |
| Solubility | Soluble in aqueous buffers (pH 7–8); limited solubility in water alone |
| Storage | -20°C (lyophilized), 2–8°C (reconstituted) |
Mechanism of Action¶
Semaglutide binds with high affinity to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor expressed on pancreatic β-cells, gastrointestinal L-cells, and brainstem nuclei. Upon binding, it activates adenylyl cyclase via Gαs, elevating intracellular cAMP and stimulating PKA-dependent insulin exocytosis in a glucose-dependent manner. Simultaneously, semaglutide suppresses glucagon secretion from pancreatic α-cells, reduces gastric emptying rate, and promotes satiety through central hypothalamic GLP-1R signaling. The structural modification — replacing Gly⁸ with Aib — confers near-complete resistance to DPP-4 enzymatic cleavage, while the C18 fatty diacid side chain attached via a γ-Glu-2×AEEA linker enables non-covalent binding to serum albumin, extending the elimination half-life to approximately 165 hours.
Research Applications¶
- Primary: Type 2 diabetes mellitus research — GLP-1 receptor pharmacology, glucose homeostasis, β-cell function
- Secondary: Obesity and weight management studies, cardiovascular outcomes research, non-alcoholic steatohepatitis (NASH) models
- Model Systems: In vitro (INS-1 cells, isolated islets), in vivo rodent models (diet-induced obesity, db/db mice)
Quality Control & Analytical Methods¶
- HPLC: ≥99% purity verification at 214/220 nm (C18 reversed-phase column)
- Mass Spectrometry: ESI-MS for molecular weight confirmation (4,113.6 ±1.0 Da)
- Peptide Content: Amino acid analysis (AAA) for net peptide content determination
- Endotoxin: <1 EU/mg (LAL assay)
- TFA Content: <1% (ion chromatography)
Stability & Storage¶
| Condition | Stability |
|---|---|
| -20°C (lyophilized) | 24 months |
| 4°C (lyophilized) | 6 months |
| 25°C (lyophilized) | 1 month |
| Reconstituted (4°C) | 7 days |
| Reconstituted (-20°C) | 30 days |
Key Research References¶
- Knudsen & Lau (2019) — Discovery of semaglutide: a once-weekly GLP-1 analog with extended half-life through albumin binding. J Med Chem. PMID: 30844204
- Wilding et al. (2021) — Semaglutide 2.4 mg once weekly in adults with overweight or obesity: STEP 1 randomized trial. N Engl J Med. PMID: 33567185
- Marso et al. (2016) — Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). N Engl J Med. PMID: 27633186
Source & Purchase¶
For researchers requiring research-grade SEMAGLUTIDE with full analytical documentation including HPLC, LC-MS, and Certificate of Analysis, visit the HK Peptides product page for specifications, bulk pricing, and ordering.
Related Molecules¶
- Tirzepatide — Dual GIP/GLP-1 receptor agonist
- Retatrutide — Triple GIP/GLP-1/GCG receptor agonist
- Cagrilintide — Long-acting amylin analog
- All Product Specifications
FAQ¶
Q: What purity level is standard for Semaglutide? A: HK Peptides supplies Semaglutide at ≥99% purity by HPLC with full COA documentation.
Q: How should Semaglutide be stored for research use? A: Lyophilized Semaglutide should be stored at -20°C. Reconstituted solutions at 4°C for short-term use (up to 7 days); aliquot and freeze at -20°C for longer storage.