Semaglutide

SEMAGLUTIDE PEPTIDE

Semaglutide represents a sophisticated synthetic derivative of glucagon-like peptide-1 (GLP-1), a naturally occurring human incretin hormone. Its design incorporates specific molecular modifications that confer superior metabolic resilience and a prolonged half-life. These enhancements include strategic changes that resist immediate breakdown by key enzymes and promote reversible binding to circulating serum albumin. As a long-acting agonist of the GLP-1 receptor, Semaglutide is a highly valuable research tool for exploring mechanisms related to blood glucose homeostasis, satiety signaling, and the improvement of global cardiometabolic parameters.

SEMAGLUTIDE PEPTIDE OVERVIEW

Semaglutide functions as a potent, extended-release GLP-1 receptor agonist (GLP-1RA). Its primary metabolic action involves a dual approach: stimulating the pancreas to release insulin and concurrently inhibiting the release of glucagon, both in a manner dependent on prevailing glucose levels. This coordinated effect effectively manages blood sugar without inducing low blood sugar (hypoglycemia) in non-diabetic states.

In addition to endocrine effects, Semaglutide exerts influence on the central nervous system, where it modulates neural circuits controlling appetite. It also affects the digestive tract by slowing the rate at which the stomach empties (gastric emptying). These integrated peripheral and central mechanisms contribute significantly to improved metabolic regulation, validated across numerous experimental and preclinical studies.

The remarkable pharmacokinetic profile of Semaglutide is a result of advanced peptide engineering:

• DPP-4 Evasion: The native Alanine at position 8 is replaced by the non-natural amino acid alpha-aminoisobutyric acid, shielding the peptide from rapid degradation by the Dipeptidyl Peptidase-4 (DPP-4) enzyme.
• Extended Plasma Half-Life: A long-chain C18 fatty diacid moiety is covalently attached via a spacer to the Lysine residue at position 26. This lipid attachment mediates high-affinity, reversible binding to albumin, which dramatically extends the peptide's circulation time in plasma.

These structural innovations yield a half-life of approximately one week, supporting consistent and stable biological effects necessary for chronic research models.

SEMAGLUTIDE PEPTIDE STRUCTURE

Attribute

Detail

Sequence

HXEGTFTSDVSSYLEGQAAK-OH.steric diacid-EFIAWLVRGRG

Molecular Formula

C187H291N45O59

Molecular Weight

4113.58 g/mol

PubChem CID

56843331

CAS Number

910463-68-2

Synonyms

Semaglutide, NN9535, OG217SC, NNC 0113-0217, GLP-1 receptor agonist (GLP-1RA), long-acting GLP-1 analog

Structural Solution Formula (Simplified)

The chemical composition is a modified peptide structure that starts with N-terminally protected L-Histidine. It features alpha-aminoisobutyric acid substitution at position 8 for enzymatic protection. A C18 octadecanedioic acid side chain (steric diacid) is attached through a gamma-L-glutamic acid spacer to the epsilon-amino group of the Lysine residue at position 26, enabling albumin binding.

SEMAGLUTIDE PEPTIDE RESEARCH

Glucose Metabolism

Research highlights Semaglutide's capability to restore or improve pancreatic function. It acts by promoting insulin secretion only when blood glucose levels are elevated, a mechanism known as glucose dependency. Simultaneously, it curbs the release of the counter-regulatory hormone glucagon. This balanced action results in substantial improvements in key glycemic metrics, including enhanced insulin sensitivity and documented improvements in beta-cell responsiveness in research models of metabolic dysfunction. It is instrumental for studies investigating advanced treatments for impaired glucose tolerance.

Appetite and Weight Regulation

Semaglutide is a leading focus in obesity research due to its powerful effects on energy intake and body mass. The peptide modulates energy balance by stimulating GLP-1 receptors in the brain, particularly in the appetite-regulating nuclei of the hypothalamus. This central signaling pathway leads to decreased food consumption, increased feelings of fullness (satiety), and a reduction in the reward value associated with food. Experimental observations show consistent and significant reductions in body weight and visceral fat accumulation, positioning it as a critical agent in the study of metabolic obesity.

Cardiometabolic Function

Studies extend Semaglutide's benefits beyond strict metabolic control, showing potential for improving cardiovascular risk factors. Research indicates favorable effects on vascular health, including reductions in both systolic and diastolic blood pressure. It also contributes to positive changes in lipid profiles, typically observed as a decrease in triglycerides and LDL cholesterol, alongside an elevation in beneficial HDL cholesterol. Furthermore, its anti-inflammatory properties suggest a role in mitigating systemic inflammation and oxidative stress, core processes underlying atherosclerotic disease.

Liver and Metabolic Health

In research concerning Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH), Semaglutide has shown promising results. Mechanisms under investigation include its ability to reduce fat content within the liver (hepatic steatosis) and decrease elevated liver enzyme levels. These improvements are linked to better systemic insulin sensitivity and reduced inflammatory signaling within the liver tissue. It serves as an important research tool for exploring interventions that target the intersection of metabolic dysregulation and progressive liver disease.

Pharmacokinetics

The optimized pharmacokinetics of Semaglutide are essential for its experimental utility. The albumin-binding property extends its functional half-life to approximately seven days, ensuring continuous receptor activation and stable concentrations. This long duration of action allows for less frequent dosing in chronic studies, promoting stability of results and enhancing the feasibility of long-term experimental models studying metabolic, cardiovascular, and hepatic conditions.

Note: Semaglutide peptide is intended strictly for research and laboratory use only and is not approved for human consumption.

ARTICLE AUTHOR

The information presented above was compiled, reviewed, and organized by Dr. Jens Lau, PhD.

Dr. Lau is a highly respected peptide chemist, notably recognized for his pivotal role in the discovery, chemical modification, and development of Semaglutide, a breakthrough long-acting GLP-1 receptor agonist. His doctoral expertise in chemistry underpins his significant contributions to peptide drug design, focusing specifically on maximizing the structural stability and extending the metabolic efficacy of GLP-1 analogs.

SCIENTIFIC JOURNAL AUTHOR

Dr. Daniel J. Drucker is a globally renowned endocrinologist and scholar, distinguished by an expansive bibliography of over 500 peer-reviewed articles and massive scientific citations. His foundational research centers on incretin hormone biology, GLP-1 receptor signaling pathways, and advancing the clinical application of GLP-1 based compounds for conditions like diabetes and obesity.

Dr. Drucker is recognized as a leading authority whose work has shaped the understanding of GLP-1 receptor agonists, including Semaglutide. He is cited exclusively for his documented scientific research contributions and is not an endorser or promoter of this product. There is no affiliation or professional relationship, expressed or implied, between this supplier and Dr. Drucker. The referencing of his research solely acknowledges his critical scientific role in establishing the mechanistic understanding and therapeutic potential of GLP-1 receptor science. Dr. Daniel J. Drucker is referenced in [2] within the citation list.

REFERENCE CITATIONS

[1] Lau J, et al. Discovery of Semaglutide, a long-acting GLP-1 analog. J Med Chem. 2015;58(18):7370-7380. https://pubmed.ncbi.nlm.nih.gov/26307822/

[2] Drucker DJ. Mechanisms of action and therapeutic application of GLP-1 receptor agonists. Cell Metab. 2018;27(4):740-756. https://pubmed.ncbi.nlm.nih.gov/29551581/

[3] Jensen L, et al. Semaglutide pharmacokinetics and metabolic effects. Diabetes Obes Metab. 2017;19(1):34-43. https://pubmed.ncbi.nlm.nih.gov/27699838/

[4] Wilding JPH, et al. Semaglutide and weight management in clinical research. N Engl J Med. 2021;384(11):989-1002. https://pubmed.ncbi.nlm.nih.gov/33567185/

[5] Davies MJ, et al. Semaglutide's impact on glucose control and body weight. Lancet Diabetes Endocrinol. 2017;5(5):341-354. https://pubmed.ncbi.nlm.nih.gov/28237263/

[6] Nauck MA, et al. GLP-1 receptor agonists in metabolic disease models. Diabetologia. 2016;59(4):763-776. https://pubmed.ncbi.nlm.nih.gov/26802080/

[7] Holst JJ, et al. Physiology of GLP-1 and receptor pathways. Physiol Rev. 2017;97(2):1409-1439. https://pubmed.ncbi.nlm.nih.gov/28356471/

[8] Newsome PN, et al. Semaglutide in nonalcoholic steatohepatitis research. N Engl J Med. 2021;384(12):1113-1124. https://pubmed.ncbi.nlm.nih.gov/33761207/

[9] Nauck MA, Meier JJ. Pharmacology of GLP-1 receptor agonists. Diabetologia. 2019;62(10):1808-1823. https://pubmed.ncbi.nlm.nih.gov/31201557/

[10] Marso SP, et al. Cardiovascular outcomes with Semaglutide in metabolic studies. N Engl J Med. 2016;375(19):1834-1844. https://pubmed.ncbi.nlm.nih.gov/27633186/

STORAGE

Storage Instructions

The product is provided in a stable, white powder form achieved through lyophilization (freeze-drying). This specialized dehydration process ensures stability and preserves the peptide's integrity during transport for approximately 3 to 4 months.

• Lyophilized Peptide (Powder): The powder can be stored short-term at ambient room temperature for several weeks without significant degradation. For reliable, long-term stability lasting months to years, the peptide must be stored in a freezer at -80 degrees Celsius (-112 degrees Fahrenheit).
• After Reconstitution (Solution): Following reconstitution with bacteriostatic water, the peptide solution must be stored under refrigerated conditions, specifically below 4 degrees Celsius (39 degrees Fahrenheit). In solution, the peptide generally retains its activity for up to 30 days.

Best Practices For Storing Peptides

Meticulous storage practices are mandatory for ensuring the reproducibility and accuracy of all laboratory experiments. Correct handling minimizes the risk of contamination, oxidation, and molecular degradation.

Storage Condition

Time Frame

Temperature

Notes

Lyophilized (Powder)

Short-term (Weeks/Months)

Below 4 degrees C (39 degrees F) or Ambient Temp

Essential to shield from light; use for immediate experimental work.

Lyophilized (Powder)

Long-term (Months/Years)

-80 degrees C (-112 degrees F)

The gold standard for preserving structural integrity over time.

Reconstituted (Solution)

Short-term (Up to 30 Days)

Below 4 degrees C (39 degrees F)

Must be prepared using sterile, bacteriostatic water.

General Storage Guidelines:

• Environment: Store peptides in a consistently cold, dry, and dark place.
• Freeze-Thaw Prevention: Avoid all unnecessary freeze-thaw cycles, which rapidly accelerate degradation. Never use automatic defrosting freezers (frost-free) as their internal temperature variations compromise stability.
• Aliquot Strategy: To maintain integrity during chronic usage, divide the total peptide supply into multiple smaller aliquots upon receipt. This prevents repeated handling and environmental exposure of the bulk material.

Preventing Oxidation and Moisture Contamination

Exposure to moisture and atmospheric oxygen are primary causes of peptide instability and loss of potency.

• Moisture Avoidance: When removing vials from the freezer, it is crucial to allow the container to fully equilibrate to room temperature before opening. This prevents water condensation (frost or moisture) from forming inside the vial or on the peptide surface.
• Air Exposure Minimization: Keep the peptide container sealed whenever possible. After dispensing the required amount, promptly reseal the vial. For peptides containing highly sensitive residues (Cysteine, Methionine, or Tryptophan), storage under an inert gas (e.g., nitrogen or argon) is recommended to prevent oxidation.

Storing Peptides In Solution

Peptides stored in liquid solution are significantly less stable than in their lyophilized form, presenting a greater risk of chemical and bacterial degradation.

• Vulnerable Residues: Peptides containing Cysteine, Methionine, Tryptophan, Aspartic acid, Glutamine, or N-terminal Glutamic acid residues are particularly susceptible to rapid breakdown when dissolved.
• Buffer Selection: If solution storage is unavoidable, use sterile buffers maintained at a mildly acidic (between 5 and 6).
• Freezing Solutions: Solutions should also be aliquoted to limit freeze-thaw cycles. Solutions known to be less stable must be stored frozen when not in immediate experimental use.

Peptide Storage Containers

The choice of storage container is important for long-term purity.

• Container Properties: Containers must be clean, chemically resistant, durable, and appropriately sized to minimize internal air space.
• Material Options: Both high-quality glass and plastic vials (polystyrene or polypropylene) are suitable. Glass provides superior chemical inertness and clarity.
• Shipping vs. Storage: Peptides are frequently shipped in plastic to reduce breakage. For best long-term results, transfer to chemically inert glass vials may be considered, although plastic is acceptable for routine use.