This is a working overview of 二肽基肽酶-4, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-05-20. Anything still debated is marked as such rather than presented as settled.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
Semaglutide is a synthetic peptide of thirty-one amino acids that shares roughly ninety-four percent sequence identity with human glucagon-like peptide-1. Two substitutions resist enzymatic cleavage by dipeptidyl peptidase-4, and a fatty diacid side chain attached through a linker promotes binding to serum albumin. That albumin binding slows renal clearance and extends the circulating half-life from minutes to approximately one week. The structural changes are well established in the published literature. Whether the same modifications affect receptor signalling bias in ways that matter clinically remains an open question.
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。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
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.
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.
If, for example, the Sun were replaced by a black hole of equal mass, the orbits of the planets would be essentially unaffected. Seasons are not caused by Earth being closer to the Sun in the summer than in the winter, but by the effects of Earth's 23.4-degree axial tilt. Each hemisphere is tilted towards the Sun in its respective summer, resulting in longer days and more perpendicular sunlight, with the opposite being true in the winter. Earth reaches the point in its orbit closest to the Sun in January, and it reaches the point farthest from the Sun in July, so the slight contribution of orbital eccentricity opposes the temperature trends of the seasons in the Northern Hemisphere. When a meteor or spacecraft enters the atmosphere, the heat of entry is not primarily caused by friction, but by adiabatic compression of air in front of the object. Egg balancing is possible on every day of the year, not just the vernal equinox. The Fisher Space Pen was not commissioned by NASA at a cost of millions of dollars, while the Soviets used pencils. Pencils posed a major risk to astronauts due to the release of substances such as shavings and pencil lead being a flight hazard. The pen was independently developed by Paul C. Fisher, founder of the Fisher Pen Company, with $1 million of his own funds (equivalent to $10 million in 2025). NASA tested and approved the pen for space use, then purchased 400 pens at $6 per pen (equivalent to $58 in 2025). The Soviet Union subsequently also purchased the Space Pen for its Soyuz spaceflights.
== Treatment == Solar purpura does not require treatment and may resolve on its own within weeks or months. The lesions may also be permanent. Many people seek treatment for cosmetic purposes. There have been several studies on possible future treatments. A common treatment involves Retinoic acid and other vitamin A derivatives in an attempt to increase dermal thickness and prevent extravasation of red blood cells. The most common treatment is to avoid UV exposure, apply sunscreen, and wear long-sleeved clothing.
=== Development === Scandal was renewed for a fifth season on May 7, 2015, by ABC. The series will continue to air at Thursdays in the timeslot 9:00 p.m. E.T. like the previous season, as it was moved to the timeslot to make room for ShondaLand Production Company's new TV series, How to Get Away with Murder. Production began on May 21, 2015, when Rhimes announced on Twitter that the writers were in full swing mapping the fifth season. The remaining fall schedule for ABC was announced on November 16, 2015, where it was announced that Scandal would air nine episodes in the fall with the fall finale to air on November 19, 2015, just like the rest of ABC's primetime lineup "TGIT" Grey's Anatomy and How To Get Away with Murder, which was the same last year. The remaining 12 episodes will air after the winter break, beginning on February 11, 2016, as a result of ABC airing the television miniseries Madoff over two nights on February 3–4, 2016 in the same time-slot as Scandal and Grey's Anatomy. The show was renewed by ABC for a sixth season on March 3, 2016.
Chemical information and Biochemical information. The chemical information includes more than 2,700 metabolite structures with detailed metabolite descriptions, extensive chemical classifications, synthesis information and observed/calculated chemical properties. It also contains nearly 5,000 NMR, GC-MS and LC-MS spectra from more than 600 different metabolites. The biochemical information includes >1,600 protein (and DNA) sequences and >3,100 biochemical reactions that are linked to these metabolite entries. The ECMDB supports many different types of online queries including text searches, chemical structure searches, sequence similarity searches and spectral similarity searches. This makes it particularly useful for metabolomic researchers who are studying E. coli as a model organism. Secondary electrospray ionization (SESI-MS) can discriminate between eleven E. Coli strains thanks to the volatile organic compound profiling.
Sources: en.wikipedia.org
As a paramilitary unit, the BSAP fought in the Second Boer War and in German East Africa during the First World War, while some members were seconded to the Rhodesia Native Regiment. From 1923, Southern Rhodesia was a self-governing colony of the British Empire, but the BSAP retained its title and its position as the senior regiment of the Southern Rhodesian armed forces. One of the first casualties of the BSAP in the Second World War was Keppel Bagot Levett, born in 1919, who died in active service with the BSAP in March 1941. Between the World Wars, the Permanent Staff Corps of the Rhodesian Army consisted of only 47 men. The BSAP were trained as both policemen and soldiers until 1954.
== Wife of the heir to Austrian throne == At this time, Archduke Charles was in his twenties and did not expect to become emperor for some time, especially while Franz Ferdinand remained in good health. This changed on 28 June 1914 when the heir and his wife Sophie were assassinated in Sarajevo by Bosnian Serb nationalists. Charles and Zita received the news by telegram that day. She said of her husband, "Though it was a beautiful day, I saw his face go white in the sun." In the war that followed, Charles was promoted to General in the Austro-Hungarian army, taking command of the 20th Corps for an offensive in Tyrol. The war was personally difficult for Zita, as several of her brothers fought on opposing sides in the conflict (Prince Felix and Prince René had joined the Austrian army, while Prince Sixtus and Prince Xavier lived in France before the war and enlisted in the Belgian army.) Also her country of birth, Italy, joined the war against Austria in 1915, and so rumours of the 'Italian' Zita began to be muttered. Even as late as 1917, the German ambassador in Vienna, Count Botho von Wedel-Jarlsberg, would write to Berlin saying "The Empress is descended from an Italian princely house... People do not entirely trust the Italian and her brood of relatives." At Franz Joseph's request, Zita and her children left their residence at Schloss Hetzendorf and moved into a suite of rooms at Schönbrunn Palace. Here, Zita spent many hours with the old Emperor on both formal and informal occasions, where Franz Joseph confided in her his fears for the future.
=== Ligand removal === In many cases, as in various high-temperature catalytic applications of Au, the removal of the capping ligands produces more desirable physicochemical properties. The removal of ligands from colloidal gold while maintaining a relatively constant number of Au atoms per Au NP can be difficult due to the tendency for these bare clusters to aggregate. The removal of ligands is partially achievable by simply washing away all excess capping ligands, though this method is ineffective in removing all capping ligand. More often ligand removal achieved under high temperature or light ablation followed by washing. Alternatively, the ligands can be electrochemically etched off.
Sources: en.wikipedia.org
In addition, surface-induced dissociation has been implemented with this instrument for the study of fundamental peptide fragmentation. Specifically, SID has been applied to the study of energetics and the kinetics of gas-phase fragmentation within an ICR instrument. This approach has been used to understand the gas-phase fragmentation of protonated peptides, odd-electron peptide ions, non-covalent ligand-peptide complexes, and ligated metal clusters.
==== March ==== On 13 March, the Syrian government forces launched attacks toward Suwayda, Syrian government forces in Kharbat Samar attacked residents in the city of Ara. On 19 March, clashes erupted between Syrian government forces and local defense units, including the Syrian National Guard, on multiple fronts around Suwayda, encompassing Tal Hadid and villages such as Walgha and Mansoura, and involving heavy and medium weaponry. A day later, Israeli airstrikes targeted several positions of Syrian government forces at Izraa in Daraa Governorate, including command and control centres, supply depots, and facilities held by the 40th Battalion of the Syrian Army, in retaliation to the escalation of hostilities. On 25 March, a National Guard member was injured during clashes in the city of Era, in southern Suwayda.
In order to remove the thin and well preserved skin slices and strips from the donor, surgeons use a special surgical instrument called a dermatome. This usually produces a split-thickness skin graft, which contains the epidermis with only a portion of the dermis. The dermis left behind at the donor site contains hair follicles and sebaceous glands, both of which contain epidermal cells which gradually proliferate out to form a new layer of epidermis. The donor site may be extremely painful and vulnerable to infection. There are several ways to treat donor site pain. These include subcutaneous anesthetic agents, topical anesthetic agents, and certain types of wound dressings.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。