The short version of 长效肽设计 fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-02-15. Anything still debated is marked as such rather than presented as settled.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
Storage at minus 20 degrees Celsius or lower in a desiccated container preserves the peptide for extended periods, while working solutions are commonly held at two to eight degrees Celsius for short intervals. Light exposure and repeated freeze-thaw cycles accelerate degradation, so dividing material into single-use aliquots is generally recommended. Adsorption to glass and plastic surfaces can lower the measured concentration of dilute solutions, particularly below one milligram per millilitre. The degradation routes most often reported for GLP-1 analogues are deamidation, methionine oxidation, and backbone hydrolysis. Relative rates under specific conditions are frequently described only for individual formulations.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 or 280 nanometres is widely used to assess purity and to resolve related impurities. Liquid chromatography coupled to mass spectrometry confirms identity through the protonated molecular ion and fragment ions formed in tandem experiments. Capillary electrophoresis and peptide mapping after enzymatic digestion supply complementary information on charge variants and modification sites. Circular dichroism and nuclear magnetic resonance can report on secondary structure in solution. Absolute quantification usually depends on an external standard, and reported purity depends on the detection wavelength and integration parameters chosen.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | Parent peptide; salt forms also reported |
| Molecular mass | about 4113.6 Da | Average mass of the free peptide |
| Peptide length | 31 amino acids | Backbone related to GLP-1(7-37) |
| Key substitution | Aib at position 8 | Blocks DPP-4 cleavage |
| Albumin binding | Via C-18 diacid side chain | Prolongs circulation time |
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L cells after food intake. The molecule is a 31-amino-acid backbone modified at three positions to resist cleavage by dipeptidyl peptidase-4, the enzyme that degrades native GLP-1 within minutes. A lysine residue at position 26 carries a linker and a C18 fatty diacid, which promotes binding to serum albumin and slows renal clearance. These changes extend the circulating half-life from roughly two minutes to about one week in humans.
The sequence incorporates alpha-aminoisobutyric acid at position 8, replacing the alanine found in the natural hormone. This substitution blocks the primary DPP-4 recognition site and contributes most of the enzymatic stability. Albumin binding further protects the peptide and reduces the frequency of administration required to maintain active plasma levels. Because the fatty acid chain increases lipophilicity, the compound is formulated as a solution rather than a simple aqueous buffer. Researchers describe the design as an incremental optimization of earlier GLP-1 analogs rather than a wholly new scaffold.
Reported molecular weight is approximately 4113.6 daltons for the free base, and the peptide is supplied as a lyophilized powder or in buffered liquid form depending on the intended use. It is freely soluble in water when formulated with appropriate excipients, though the unconjugated peptide shows limited stability at neutral pH over long periods. Analytical characterization typically relies on reversed-phase high-performance liquid chromatography and mass spectrometry. Purity specifications for research-grade material commonly exceed ninety-five percent by area. Isotopic and impurity profiles differ between suppliers.
doi:10.1016/S0733-8627(05)70156-5. PMID 11130936. Chantelau E., Schiffers T., Schutze J., Hansen B. (1997). "Effect of patient-selected intensive insulin therapy on quality of life". Patient Education and Counseling. 38 (2): 167–713. doi:10.1016/S0738-3991(96)00964-0. PMID 9128618.{{cite journal}}: CS1 maint: multiple names: authors list (link) Crawford L.M., Sinha R.N., Odell R.M., Comi R.J. (2000). "Efficacy of insulin pump therapy: mealtime delivery is the key factor". Endocrine Practice. 6 (3): 239–43. doi:10.4158/EP.6.3.239. PMID 11421538.{{cite journal}}: CS1 maint: multiple names: authors list (link) The DCCT Research Group. JAMA. 1997;227(5):374-4 Skyler J.S. Diabtes Technol Ther. 2000. The DCCT Research Group. Progression of retinopathy with intensive versus conventional treatment in the diabetes control and complications trial. 1994. The DCCT/EDIC Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. NEJM 2005; 353(25): 2643–2653. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus Diabetes Care 2001; 24: 1. Kaufman FR (2001). "A Pilot Study of the Continuous Glucose Monitoring System: Clinical decisions and glycemic control after its use in pediatric type 1 diabetic subjects". Diabetes Care. 24 (12): 2030–4. doi:10.2337/diacare.24.12.2030. PMID 11723078. Floyd J.C., Cornell R.G.; et al. (1993). "A prospective study identifying risk factors for discontinuance of insulin pump therapy".
== Culture and organization == In early times, an ataman (later called hetman) commanded a Cossack band. He was elected by the Host members at a Cossack rada, as were the other important officials: the judge, the scribe, the lesser officials, and the clergy. The ataman's symbol of power was a ceremonial mace, a bulava. Today, Russian Cossacks are led by atamans, and Ukrainian Cossacks by hetmans.
== Gene expression == The gene from which this enzyme is synthesized is mostly expressed in the liver, with some expression in the kidneys, skeletal muscle, and brain. It is also expressed in melanocytes, synovium, placenta, breasts, fetal liver and heart.
Many pharmaceutical products are sensitive to heat or cold. Controlled distribution systems and sometimes cold chains are required. A mail order or online pharmacy usually ships orders by mail services or by small parcel carrier. The shipment is not temperature-controlled and it may sit in a mail box upon delivery. Conditions can include high or low temperatures outside of the recommended storage conditions for certain products. For example, the USFDA found that the temperature in a steel mailbox painted black could reach 136 °F (58 °C) in full sun while the ambient air temperature was 101 °F (38 °C). Insulated mailing envelopes are sometimes used. Larger shipments are sent in insulated shipping containers with dry ice or gel packs. A digital temperature data logger or a time temperature indicator is often enclosed to monitor the temperature inside the container for its entire shipment.
Sources: en.wikipedia.org
== Interactions == Combination with selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, serotonin releasing agents, and serotonin receptor agonists may lead to potentially lethal serotonin syndrome. Combination with MAOIs may also result in an adrenergic storm. Use of tapentadol with alcohol or other central nervous system depressants such as benzodiazepines, barbiturates, nonbenzodiazepines, phenothiazines, gabapentinoids and other opiates may result in increased impairment, sedation, respiratory depression, and death. Tapentadol is partially metabolized by the hepatic enzymes CYP2C9, CYP2C19, and CYP2D6 so it innately has interactions with drugs that enhance or repress the activity/expression of one or more of these enzymes, as well as with substrates of these enzymes (due to competition for the enzyme); some enzyme mediators/substrates require dosing adjustments to one or both medications. The combination of tapentadol and alcohol may result in increased plasma concentrations of tapentadol and produce respiratory depression to a degree greater than the sum of the two drugs when administered separately; patients should be cautioned against alcohol consumption when taking tapentadol as the combination may be fatal. Tapentadol should be used with caution in patients who are taking one or more anticholinergic drugs, as this combination may result in urine retention (which can result in serious renal damage and is considered a medical emergency).
In November 2021, the US FDA approved pembrolizumab for the adjuvant treatment of people twelve years of age and older with stage IIB or IIC melanoma following complete resection. In November 2021, the US FDA approved pembrolizumab for the adjuvant treatment of renal cell carcinoma for people at intermediate-high or high risk of recurrence following nephrectomy. Approval was based on KEYNOTE-564, a multicenter, randomized (1:1), double-blind, placebo-controlled trial in 994 participants with intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease. In March 2022, the US FDA approved pembrolizumab for the treatment of advanced endometrial cancer. In January 2023, the US FDA approved pembrolizumab for adjuvant treatment following resection and platinum-based chemotherapy for stage IB (T2a ≥ 4 cm), II, or IIIA non-small cell lung cancer. In October 2023, the US FDA approved pembrolizumab to be used with gemcitabine and cisplatin for locally advanced unresectable or metastatic biliary tract cancer. In January 2024, the US FDA approved pembrolizumab, in combination with chemoradiotherapy for the treatment of people with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer. In June 2024, the US FDA approved pembrolizumab with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for adults with primary advanced or recurrent endometrial carcinoma.
Similarly, mixing starch into concentrated sulfuric acid gives elemental carbon and water. The effect of this can also be seen when concentrated sulfuric acid is spilled on paper. Paper is composed of cellulose, a polysaccharide related to starch. The cellulose reacts to give a burnt appearance in which the carbon appears much like soot that results from fire. Although less dramatic, the action of the acid on cotton, even in diluted form, also destroys the fabric.
Sources: en.wikipedia.org
It belongs to the incretin mimetic class and acts as a long-acting glucagon-like peptide-1 receptor agonist. The class includes several peptides with different half-lives and routes of administration.
The side chain enables reversible binding to albumin in the bloodstream, which protects the peptide from rapid renal clearance. This extends the interval between administrations compared with unmodified GLP-1.
No. It shares much of the native sequence but carries substitutions and an added side chain. These changes increase stability against enzymatic breakdown.
Filtering removes particulate matter that can block columns or scatter light. A 0.22 micrometre membrane is typical, and the filter material should be checked for peptide adsorption.