Semaglutide

SEMAGLUTIDE PEPTIDE OVERVIEW

Semaglutide is a highly potent, synthetic analog of the naturally occurring human incretin hormone glucagon-like peptide-1 (GLP-1). Developed to overcome the rapid degradation of endogenous GLP-1, Semaglutide incorporates specific molecular modifications that significantly extend its half-life and biological availability. These structural refinements allow the peptide to resist enzymatic breakdown by dipeptidyl peptidase-4 (DPP-4) and facilitate high-affinity binding to serum albumin. In the field of metabolic research, Semaglutide is a primary subject for investigating glycemic regulation, neuro-endocrine control of appetite, and long-term cardiometabolic stability.

As a selective GLP-1 receptor agonist, Semaglutide functions by stimulating the glucose-dependent secretion of insulin while simultaneously inhibiting the release of glucagon. This dual action facilitates homeostatic blood glucose management. Additionally, the peptide influences the central nervous system to modulate satiety signals and slows gastric motility, making it a critical tool for studying the complex mechanisms of energy balance and metabolic disorders.

SEMAGLUTIDE PEPTIDE STRUCTURE

The structural integrity of Semaglutide is defined by its specific amino acid sequence and a unique fatty acid side chain that enables its long-acting profile.

• Sequence: Histidine-alpha-aminoisobutyric acid-Glutamic acid-Glycine-Threonine-Phenylalanine-Threonine-Serine-Aspartic acid-Valine-Serine-Serine-Tyrosine-Leucine-Glutamic acid-Glycine-Glutamine-Alanine-Alanine-Lysine(AEEAc-AEEAc-gamma-Glu-17-carboxyheptadecanoyl)-Glycine-Glutamic acid-Phenylalanine-Isoleucine-Alanine-Tryptophan-Leucine-Valine-Arginine-Glycine-Arginine-Glycine
• Structural Formula: C187 H291 N45 O59
• Molecular Weight: 4113.58 g/mol
• PubChem CID: 56843331
• CAS Number: 910463-68-2
• Synonyms: NN9535, OG217SC, NNC 0113-0217, GLP-1 receptor agonist (GLP-1RA)

Property

Details

Peptide Class

GLP-1 Receptor Agonist

Modification 1

alpha-aminoisobutyric acid at position 8 (DPP-4 resistance)

Modification 2

C18 fatty diacid at Lys26 (Albumin binding)

Research Utility

Diabetes, Obesity, NASH, Cardiovascular Health

Solubility

Soluble in water or saline

SEMAGLUTIDE PEPTIDE RESEARCH

Glucose Metabolism and Insulin Sensitivity

Semaglutide is widely researched for its ability to optimize glucose homeostasis. It acts in a glucose-dependent manner, meaning it stimulates insulin release only when blood sugar levels are elevated. This reduces the risk of research-related hypoglycemia. Studies demonstrate that Semaglutide can preserve pancreatic beta-cell function and improve overall insulin sensitivity, providing insights into the reversal of metabolic dysfunction.

Appetite Modulation and Weight Dynamics

In neurological research, Semaglutide has shown the ability to cross the blood-brain barrier partially or act via the circumventricular organs to target the hypothalamus. By activating specific GLP-1 receptors, it suppresses hunger signals and enhances satiety. Research in various models shows a consistent reduction in caloric intake and a shift in food preference away from high-fat options, leading to significant reductions in adipose tissue mass.

Cardiovascular and Systemic Health

Semaglutide research extends into the cardiovascular system, where it has been observed to influence blood pressure regulation and lipid profiles. By reducing systemic inflammation and oxidative stress within the vascular endothelium, the peptide is a candidate for studies involving atherosclerosis and chronic heart failure. It effectively lowers LDL cholesterol and triglycerides while supporting vascular flexibility.

Hepatic Research (NAFLD and NASH)

Emerging studies highlight Semaglutide’s role in liver health. In models of nonalcoholic fatty liver disease, the peptide helps reduce hepatic fat accumulation (steatosis) and decreases markers of liver inflammation. These hepatoprotective effects are likely a secondary result of improved systemic lipid metabolism and weight reduction.

Pharmacokinetics

The pharmacokinetic profile of Semaglutide is defined by its seven-day half-life. This is achieved through the substitution of alanine with alpha-aminoisobutyric acid at the second position, which prevents cleavage by the DPP-4 enzyme. Furthermore, the attachment of a fatty acid chain allows the peptide to hitchhike on albumin proteins in the bloodstream, slowing its renal clearance.

ARTICLE AUTHOR

The information presented above was compiled, reviewed, and organized by Dr. Jens Lau, PhD. Dr. Lau is a peptide chemist best known for his instrumental role in the discovery and molecular refinement of Semaglutide, a long-acting GLP-1 receptor agonist. Holding a doctorate in chemistry, he has made significant contributions to peptide drug development, with a focus on improving the structural stability and metabolic performance of GLP-1 analogs.

SCIENTIFIC JOURNAL AUTHOR

Dr. Daniel J. Drucker is a distinguished endocrinologist and academic with more than 500 peer-reviewed publications and extensive scientific citations. His pioneering research centers on incretin biology, GLP-1 receptor signaling, and the advancement of GLP-1–based therapeutics for metabolic conditions such as diabetes and obesity. Dr. Drucker is cited as a leading authority in the study of GLP-1 receptor agonists, including Semaglutide. He is referenced solely for his scientific contributions and not as an endorser or promoter of this product.

REFERENCE CITATIONS

1. Lau J, et al. Discovery of Semaglutide, a long-acting GLP-1 analog. J Med Chem. 2015;58(18):7370-7380.
2. Drucker DJ. Mechanisms of action and therapeutic application of GLP-1 receptor agonists. Cell Metab. 2018;27(4):740-756.
3. Jensen L, et al. Semaglutide pharmacokinetics and metabolic effects. Diabetes Obes Metab. 2017;19(1):34-43.
4. Wilding JPH, et al. Semaglutide and weight management in clinical research. N Engl J Med. 2021;384(11):989-1002.
5. Davies MJ, et al. Semaglutide's impact on glucose control and body weight. Lancet Diabetes Endocrinol. 2017;5(5):341-354.
6. Nauck MA, et al. GLP-1 receptor agonists in metabolic disease models. Diabetologia. 2016;59(4):763-776.
7. Holst JJ, et al. Physiology of GLP-1 and receptor pathways. Physiol Rev. 2017;97(2):1409-1439.
8. Newsome PN, et al. Semaglutide in nonalcoholic steatohepatitis research. N Engl J Med. 2021;384(12):1113-1124.
9. Nauck MA, Meier JJ. Pharmacology of GLP-1 receptor agonists. Diabetologia. 2019;62(10):1808-1823.
10. Marso SP, et al. Cardiovascular outcomes with Semaglutide in metabolic studies. N Engl J Med. 2016;375(19):1834-1844.

STORAGE

Storage Instructions

All products are produced through a lyophilization (freeze-drying) process, which preserves stability during shipping for approximately 3 to 4 months. After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator to maintain their effectiveness. Once mixed, they remain stable for up to 30 days.

Lyophilization, also known as cryodesiccation, is a specialized dehydration method in which peptides are frozen and exposed to low pressure. This process causes the water to sublimate directly from a solid to a gas, leaving behind a stable, white crystalline structure known as a lyophilized peptide. The resulting powder can be safely kept at room temperature until it is reconstituted.

For extended storage periods lasting several months to years, it is recommended to keep peptides in a freezer at -80 degrees Celsius (-112 degrees Fahrenheit). Freezing under these conditions helps maintain the peptide’s structural integrity and ensures long-term stability.

Best Practices For Storing Peptides

Proper storage of peptides is critical to maintaining the accuracy and reliability of laboratory results. Following correct storage procedures helps prevent contamination, oxidation, and degradation. Upon receipt, peptides should be kept cool and shielded from light. For short-term use, refrigeration below 4 degrees Celsius (39 degrees Fahrenheit) is suitable. Lyophilized peptides generally remain stable at room temperature for several weeks.

Preventing Oxidation and Moisture Contamination

It is essential to protect peptides from exposure to air and moisture. Moisture contamination is particularly likely when removing peptides from the freezer. To avoid condensation, always allow the vial to reach room temperature before opening. Minimize air exposure by keeping the container closed as much as possible. Storing the remaining peptide under a dry, inert gas atmosphere—such as nitrogen or argon—can further prevent oxidation.

Storing Peptides In Solution

Peptide solutions have a significantly shorter shelf life than lyophilized forms. If storage in solution is unavoidable, use sterile buffers with a pH between 5 and 6. The solution should be divided into aliquots to minimize freeze-thaw cycles. Under refrigerated conditions at 4 degrees Celsius, most peptide solutions remain stable for up to 30 days.

Peptide Storage Containers

Containers must be clean, clear, durable, and chemically resistant. High-quality glass vials provide the best overall characteristics for storage, offering clarity and chemical inertness. Plastic vials made from polypropylene are also acceptable due to their chemical resistance.

Peptide Storage Guidelines: General Tips

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce oxidation risks.
• Protect peptides from light to prevent structural changes.
• Divide peptides into aliquots based on experimental needs.s